Replikin peptides and antibodies therefore

ABSTRACT

The present invention provides a new class of peptides related to rapid replication and their use in diagnosing, preventing and treating disease.

CROSS REFERENCE TO OTHER APPLICATIONS

[0001] This application is a Continuation-In-Part of Application No.U.S. Ser. No. 10/105,232, filed Mar. 26, 2002, which is aContinunation-In-Part of U.S. Ser. No. 09/984,057, filed Oct. 26, 2001,which claims priority from Provisional Applications 60/303,396, filedJul. 9, 2001 and 60/278,761 filed Mar. 27, 2001, the subject matter ofwhich is incorporated herein by reference.

FIELD OF THE INVENTION

[0002] This invention relates to the identification and use ofReplikins, a newly discovered class of peptides that share structuralcharacteristics. In particular, this invention relates to Replikinswhich have been found in viruses, bacteria, fungus, cancer associatedproteins, plants and unicellular parasites and their use as targets inthe development of methods of treating or preventing diseases. Further,this invention relates to the use of Replikins in the detection of thesediseases. Also this invention relates to the use of Replikins tostimulate growth of plants used for food.

INTRODUCTION AND BACKGROUND OF THE INVENTION

[0003] Rapid replication is characteristic of virulence in certainbacteria, viruses and malignancies, but no chemistry common to rapidreplication in different organisms has been described previously. Thispatent application discloses a new class of protein structures relatedto rapid replication. A new family of conserved small proteins relatedto rapid replication, named Replikins, which are used to predict andcontrol rapid replication in multiple organisms and diseases and toinduce rapid replication in plant and animal life.

[0004] We constructed an algorithm search for Replikins. In applying thealgorithm invented herein not only was the function of the epitoperevealed—rapid replication, but an entire family of homologues whosefunction is related to rapid replication was discovered, which we namedReplikins.

[0005] The algorithm is based on the following: 1) Evidence that theimmune system looks to parts rather than a whole protein in recognition.Protein chains are first hydrolyzed by the immune system into smallerpieces, frequently six (6) to ten (10) amino acids long, as part of theimmune systems' process of recognition of foreign structures againstwhich it may mount an immune defense. By way of example, the immunesystem recognizes the presence of disease by chopping up proteins of thedisease agent into smaller peptide sequences and reading them. Thisprinciple is used as a basis for the algorithm with which to search forhomologues of the malignin cancer epitope, once the structure of theepitope was known; 2) The specific structure of the malignin epitope, inwhich two of the three lysines (K's) are eight residues apart is inaccordance with the apparent ‘rules’ used by the immune system forrecognition referred to above (6-10 amino acids long); 3) The fact thatthe malignin cancer epitope was shown to be a very strong antigen, thatis—a generator of a strong immune response; that there are three lysines(K's) in the 10-mer peptide glioma Replikin and that K's are known tobind frequently to DNA and RNA as potential anchors for the entry ofviruses; and 4) One histidine (H) is included in the sequence of themalignin epitope, between the two K's which are eight (8) residuesapart, suggesting a connection to the metals of redox systems which arerequired to provide the energy for replication.

[0006] Engineered enzymes and catalytic antibodies, possessing tailoredbinding pockets with appropriately positioned functional groups havebeen successful in catalyzing a number of chemical transformations,sometimes with impressive efficiencies. Just as two or more separateproteins with specific and quite different functions are now oftenrecognized to be synthesized together by organisms, and then separatelycleaved to ‘go about their separate functions’, so the Replikinstructure is a unique protein with a unique function that appears to berecognized separately by the immune system and may be now rationallyengineered—e.g. synthesized to produce a functional unit.

[0007] From a proteomic point of view, this template based on the newlydetermined glioma peptide sequence has led to the discovery of a wideclass of proteins with related conserved structures and a particularfunction, in this case replication. Examples of the increase in Replikinconcentration with virulence of a disease appear in diseases including,influenza, HIV, cancer and tomato leaf curl virus. This class ofstructures is related to the phenomenon of rapid replication inorganisms as diverse as yeast, algae, plants, the gemini curl leaftomato virus, HIV and cancer.

[0008] In addition to detecting the presence of Replikins in rapidlyreplicating organisms, we found that 1) Replikin concentration (numberof Replikins per 100 amino acids) and 2) Replikin compositions inspecific functional states dependant on rapid replication, provide thebasis for the finding that Replikins are related quantitatively as wellas qualitatively to the rate of replication of the organism in whichthey reside. Examples of these functional proofs include therelationship found between rapid replication and virulence inglioblastoma cells, between Replikins in influenza virus and theprediction of influenza pandemics and epidemics, and the relationshipbetween Replikin concentration and rapid replication in HIV.

[0009] The first functional basis for Replikins' role in rapidreplication was found in the properties of the glioma Replikin, a 10 KDpeptide called Malignin in brain glioblastoma multiforme (glioma)—a 250KD cell protein. Antimalignin antibody increased in concentration inserum (AMAS), measured by an early stage diagnostic test for cancer nowused for most or all cell types. Malignin was so named because in tissueculture the expression of this peptide and its concentration permilligram membrane protein extractable increased with increased rate ofcell division per unit time. Not only is there an increase in the amountof malignin in proportion to the cell number increase but the amount ofmalignin is enriched, that is—increased ten fold whereas the cell numberincreased only five fold.

[0010] The structure of malignin protein was determined throughhydrolysis and mass spectrometry which revealed what proved to be anovel 16 mer peptide sequence. We searched for the 16 mer peptidesequence which we have named a Glioma Replikin protein in databases forthe healthy human genome and found that it was not present in thesedatabases.

[0011] As such, the fixed requirement algorithm was used to search inother organisms for the Glioma Replikin protein or homologues thereof.Over 4,000 protein sequences in the “Pub Med” database were searched andhomologues were found in viruses and plant forms specifically associatedwith rapid replication. Homologues of such Replikin proteins occurredfrequently in proteins called ‘replicating proteins’ by theirinvestigators.

[0012] Homologues of the Replikin sequence were found in all tumorviruses (that is viruses that cause cancer), and in ‘replicatingproteins’ of algae, plants, fungi, viruses and bacteria.

[0013] That malignin is enriched ten-fold compared to the five-foldincrease in cell number and membrane protein concentration in rapidreplication of glioma cells suggests an integral relationship of theReplikins to replication. When the glioma replikin was synthesized invitro and administered as a synthetic vaccine to rabbits, abundantantimalignin antibody was produced—establishing rigourously theantigenic basis of the antimalignin antibody in serum (AMAS) test, andproviding the first potential synthetic cancer vaccine and the prototypefor Replikin vaccines in other organisms.

[0014] The demonstration of the relationship of the Replikins toreplication and the natural immune response to cancer Replikins(overriding cell type) based upon the shared specificity of cancerReplikins, permits passive augmentation of immunity with antimaligninantibody and active augmentation with synthetic Replikin vaccines.

[0015] A study of 8,090 serum specimens from cancer patients andcontrols has demonstrated that the concentration of antimaligninantibody increases with age in healthy individuals, as the incidence ofcancer in the population increases, and increases further two tothree-fold in early malignancy, regardless of cell type. In vitro thisantibody is cytotoxic to cancer cells at picograms (femtomoles) percancer cell, and in vivo the concentration of antimalignin antibodyrelates quantitatively to the survival of cancer patients. As shown inglioma cells, the stage in cancer at which cells only have beentransformed to the immortal malignant state but remain quiescent ordormant, now can be distinguished from the more active life-threateningreplicating state which is characterized by the increased concentrationof Replikins. In addition, clues to the viral pathogenesis of cancer maybe found in the fact that glioma glycoprotein 10B has a 50% reduction incarbohydrate residues when compared to the normal 10B. This reduction isassociated with virus entry in other instances and so may be evidence ofthe attachment of virus for the delivery of virus Replikins to the 10Bof glial cells as a step in the transformation to the malignant state.

[0016] The sharing of immunological specificity by diverse members ofthe class, as demonstrated with antimalignin antibody for the glioma andrelated cancer Replikins, suggests that B cells and their productantibodies may recognize Replikins by means of a similar recognition‘language’. With the discovery of the Replikins, this sharedimmunological specificity may explain what was previously difficult tounderstand: why the antimalignin antibody is elevated in all cancers,and is cytotoxic to cancer cells and related to survival of cancerpatients in most or all cell types. Thus antimalignin antibody isproduced against cancer Replikins, which share immunological specificityand which are related to the phenomenon of rapid replication, not tocell type.

[0017] A second functional basis for the Replikins' role in rapidreplication is the study of data from the past 100 years on influenzavirus hemagglutinin protein sequences and epidemiology of influenzaepidemics and pandemics. To date, only serological hemagglutinin andantibody classification, but no strain-specific conserved peptidesequences have previously been described in influenza, and no changes inconcentration and composition of any strain-specific peptide sequenceshave been described previously which correlate with epidemiologicallydocumented epidemics or rapid replication.

[0018] A four to ten-fold increase in the concentration ofstrain-specific influenza Replikins in one of each of the four majorstrains, influenza B, (A)H1N1, (A)H2N2 and (A)H3N2 was found, and thatsuch increase of Replikin concentration was related to influenzaepidemics caused specifically by each strain from 1902 to 2001. Theseincreases in concentration were then shown to be due to the reappearanceof at least one specific Replikin composition from 1 to up to 64 yearsafter its disappearance, plus the emergence of new strain-specificReplikin compositions. Previously, no strain-specific chemicalstructures were known with which to predict which strains wouldpredominate in coming influenza seasons, nor to devise annual mixturesof whole-virus strains for vaccines. The recent sharp increase in H3N2Replikin concentration (1997 to 2000), the largest in H3N2's history,and the reappearance of specific Replikin compositions which were lastseen in the high mortality H3N2 pandemic of 1968 and in the two highmortality epidemics of 1975 and 1977, but were absent for 20-25 years,together may be a warning of coming epidemics.

[0019] Synthetic Replikins are new vaccines. This high degree ofconservation of Replikin structures observed whereby the identicalstructure can persist for 100 years, or reappear after an absence offrom one to 64 years reappears indicates that what was previouslythought to be change in virulence due to random substitution of aminoacids in influenza proteins is more likely to be change due to anorganized process of conservation of Replikins. In fact, if randomsubstitutions of each amino acid occurred, the chance against an averagelength influenza Replikin sequence being conserved for one year (letalone 100) is calculated to be in the order of 2 to the 27^(th) power to1.

[0020] The significant conservation of Replikins is not unique toinfluenza virus is also present in foot and mouth disease virus type 0and in HIV, as well as in wheat.

[0021] A third functional basis for Replikins' role in rapid replicationis the increase in Replikin concentration shown to be related to rapidreplication in HIV. The Replikin concentration in the slow-growinglow-titre strain of HIV (NS1, “Bru”), prevalent in early stageinfection, was found to be one-sixth of the Replikin concentration inthe rapidly-growing high-titre strain of HIV (SI, “Lai”), prevalent inlate stage HIV infection.

[0022] Other examples are given of the relation of Replikins to rapidreplication. For example, in tomato curl leaf gemini virus, whichdevastates tomato crops, the first 161 amino acids of the ‘replicatingprotein’, which have been shown to bind to DNA, contain five Replikins.

[0023] In malaria, legendary for rapid replication, trypanosomes arereleased from the liver in tens of thousands from one trypanosome.Multiple, novel, almost ‘flamboyant’ Replikin structures withconcentrations of up to 36 overlapping Replikins per 100 amino acids arefound therein.

[0024] The increase in Replikin concentration in influenza epidemics isfunctionally comparable to the glioma Replikin's increase inconcentration during rapid replication of malignant glioma cells andcomparable to rapid replication in HIV and in a diverse range of otherorganisms. Replikins thus are associated with and appear to be part ofthe structural bases of rapid replication in different organisms.

[0025] Replikin concentration and composition therefore provide newmethods to detect and to control the process of replication, which iscentral to the survival and dominance of each biological population. Thediscovery of these new proteins related to rapid replication providesnew opportunities 1) for detection of pathogens by qualitative andquantitative determinations of Replikins, 2) for the control of a broadrange of diseases in which rapid replication is a key factor bytargeting native Replikins and by using synthetic Replikins as vaccines,and 3) for the use of Replikins to foster growth of algal and plantfoods.

[0026] There is a significant number of diseases and pathogens whichhave proved difficult to detect and treat and for which there is noeffective vaccine. Thus, for each disorder there is a need fordeveloping a target that will provide effective methods of detecting,treating or preventing these diseases and pathogens.

SUMMARY OF THE INVENTION

[0027] The present invention provides a method for identifyingnucleotide or amino acid sequences that include a Replikin sequence. Themethod is referred to herein as a 3-point-recognition method. By use ofthe “3-point recognition” method, namely, peptides comprising from 7 toabout 50 amino acids including:

[0028] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue;

[0029] (2) at least one histidine residue; and

[0030] (3) at least 6% lysine residues (Replikin)—constituting a newclass of peptides was revealed in algae, yeast, flungi, amoebae,bacteria, plant and virus proteins having replication, transformation,or redox functions.

[0031] In one aspect of the invention there are provided isolated orsynthesized peptides containing a Replikin sequence. The peptidescomprise from 7 to about 50 amino acids including:

[0032] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residues;

[0033] (2) at least one histidine residue; and

[0034] (3) at least 6% lysine residues.

[0035] The present invention also provides methods for detecting thepresence of a contaminating organism in a body sample or environmentalsample comprising:

[0036] (1) isolating nucleic acids from the body sample or environmentalsample;

[0037] (2) screening the nucleic acids for the presence of a Replikinstructure; and

[0038] (3) correlating the presence of a Replikin structure with thepresence of the contaminating organism.

[0039] In another aspect of the invention there is provided a processfor stimulating the immune system of a subject to produce antibodiesthat bind specifically to a Replikin sequence, said process comprisingadministering to the subject an effective amount of a dosage of acomposition comprising at least one Replikin peptide. One embodimentcomprises at least one peptide that is present in an emerging strain ofthe organism if such new strain emerges.

[0040] The present invention also provides antibodies that bindspecifically to a Replikin, as defined herein, as well as antibodycocktails containing a plurality of antibodies that specifically bind toReplikins. In one embodiment of the invention, there are providedcompositions comprising an antibody or antibodies that specifically bindto a Replikin and a pharmaceutically acceptable carrier.

[0041] In one aspect of the invention there are provided isolated, orseparated from other proteins, recombinant, or synthesized peptides orother methods containing a viral Replikin sequence. The viral Replikinpeptides comprise from 7 to about 50 amino acids including:

[0042] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue;

[0043] (2) at least one histidine residue; and

[0044] (3) at least 6% lysine residues. (viral Replikin).

[0045] The present invention also provides methods for detecting thepresence of a contaminating virus in a body sample or environmentalsample comprising:

[0046] (1) isolating nucleic acids from the body sample or environmentalsample;

[0047] (2) screening the nucleic acids for the presence of a viralReplikin structure; and

[0048] (3) correlating the presence of viral Replikin structures, theirconcentration and composition, with the presence of the contaminatingvirus.

[0049] In another aspect of the invention there is provided a processfor stimulating the immune system of a subject to produce antibodiesthat bind specifically to a viral Replikin sequence, said processcomprising administering to the subject an effective amount of a dosageof a composition comprising at least one Replikin peptide. Oneembodiment comprises at least one peptide that is present in an emergingstrain of the virus if such new strain emerges.

[0050] The present invention also provides antibodies that bindspecifically to a viral Replikin, as defined herein, as well as antibodycocktails containing a plurality of antibodies that specifically bind toviral Replikins. In one embodiment of the invention, there are providedcompositions comprising an antibody or antibodies that specifically bindto a viral Replikin and a pharmaceutically acceptable carrier.

[0051] The present invention also provides therapeutic compositionscomprising one or more of isolated virus peptides having from 7 to about50 amino acids comprising:

[0052] (1) at least one lysine residue located six to ten residues froma second lysine residue;

[0053] (2) at least one histidine residue; and

[0054] (3) at least 6% lysine residues, and a pharmaceuticallyacceptable carrier.

[0055] In another aspect of the invention there is provided an antisensenucleic acid molecule complementary to a virus Replikin mRNA sequence,said Replikin mRNA sequence denoting from 7 to about 50 amino acidscomprising:

[0056] (1) at least one lysine residue located six to ten residues froma second lysine residue;

[0057] (2) at least one histidine residue; and

[0058] (3) at least 6% lysine residues.

[0059] In yet another aspect of the invention there is provided a methodof simulating the immune system of a subject to produce antibodies toviruses, said method comprising: administering an effective amount of atleast one virus Replikin peptide having from 7 to about 50 amino acidscomprising:

[0060] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue;

[0061] (2) at least one histidine residue; and

[0062] (3) at least 6% lysine residues.

[0063] In another aspect, there is provided a method of selecting avirus peptide for inclusion in a preventive or therapeutic virus vaccinecomprising:

[0064] (1) obtaining at least one isolate of each strain of a pluralityof strains of said virus;

[0065] (2) analyzing the amino acid sequence of the at least one isolateof each strain of the plurality of strains of the virus for the presenceand concentration of Replikin sequences;

[0066] (3) comparing the concentration of Replikin sequences in theamino acid sequence of the at least one isolate of each strain of theplurality of strains of the virus to the concentration of Replikinsequences observed in the amino acid sequence of each of the strains atleast one earlier time period to provide the concentration of Replikinsfor at least two time periods, said at least one earlier time periodbeing within about six months to about three years prior to step (1);

[0067] (4) indentifying the strain of the virus having the highestincrease in concentration of Replikin sequences during the at least twotime periods; and

[0068] (5) selecting at least one Replikin sequence present in thestrain of the virus peptide identified in step (4) as a peptide forinclusion in the virus vaccine.

[0069] The present invention also provides a method of making apreventive or therapeutic virus vaccine comprising:

[0070] (1) identifying a strain of a virus as an emerging strain,

[0071] (2) selecting at least one Replikin sequence present in theemerging strain as a peptide template for the virus vaccine manufacture,

[0072] (3) synthesizing peptides having the amino acid sequence of theat least one Replikin sequence selected in step (2), and

[0073] (4) combining a therapeutically effective amount of the peptidesof step (3) with a pharmaceutically acceptable carrier and/or adjuvant.

[0074] In another aspect, the invention is directed to a method ofidentifying an emerging strain of a virus for diagnostic, preventive ortherapeutic purposes comprising:

[0075] (1) obtaining at least one isolate of each strain of a pluralityof strains of the virus;

[0076] (2) analyzing the amino acid sequence of the at least one isolateof each strain of the plurality of strains of the virus for the presenceand concentration of Replikin sequences;

[0077] (3) comparing the concentration of Replikin sequences in theamino acid sequence of the at least one isolate of each strain of theplurality of strains of the virus to the concentration of Replikinsequences observed in the amino acid sequence of each of the strains atat least one earlier time period to provide the concentration ofReplikins for at least two time periods, said at least one earlier timeperiod being within about six months to about three years prior to step(1); and

[0078] (4) identifying the strain of the virus having the highestincrease in concentration of Replikin sequences during the at least twotime periods.

[0079] In yet another aspect of the invention, there is provided apreventive or therapeutic virus vaccine comprising at least one isolatedReplikin present in a protein of an emerging strain of the virus and apharmaceutically acceptable carrier and/or adjuvant.

[0080] Also provided by the present invention is a method of preventingor treating a virus infection comprising administering to a patient inneed thereof a preventive or therapeutic virus vaccine comprising atleast one isolated Replikin present in a protein of an emerging strainof the virus and a pharmaceutically acceptable carrier and/or adjuvant.

[0081] Influenza

[0082] Influenza is an acute respiratory illness of global importance.Despite international attempts to control influenza virus outbreaksthrough vaccination, influenza infections remain an important cause ofmorbidity and mortality. Worldwide influenza epidemics and pandemicshave occurred at irregular and previously unpredictable intervalsthroughout history and it is expected that they will continue to occurin the future. The impact of both pandemic and epidemic influenza issubstantial in terms of morbidity, mortality and economic cost.

[0083] Influenza vaccines remain the most effective defense againstinfluenza virus, but because of the ability of the virus to mutate andthe availability of non-human host reservoirs, it is expected thatinfluenza will remain an emergent or re-emergent infection. Globalinfluenza surveillance indicates that influenza viruses may vary withina country and between countries and continents during an influenzaseason. Virological surveillance is of importance in monitoringantigenic shift and drift. Disease surveillance is also important inassessing the impact of epidemics. Both types of information haveprovided the basis of the vaccine composition and the correct use ofantivirals. However, to date there has been only annual post hochematological classification of the increasing number of emerginginfluenza virus strains, and no specific chemical structure of theviruses has been identified as an indicator of approaching influenzaepidemics or pandemics. Currently, the only basis for annualclassification of influenza virus as active, inactive or prevalent in agiven year is the activities of the virus hemagglutinin andneuramimidase proteins. No influenza viral chemical structure has beenidentified prior to this application that can be used for quantitativewarning of epidemics or pandemics or to design more effective and safervaccines.

[0084] Because of the annual administration of influenza vaccines andthe short period of time when a vaccine can be administered, strategiesdirected at improving vaccine coverage are of critical importance.

[0085] In one aspect of the invention there are provided isolated orsynthesized influenza virus peptides containing a Replikin sequence. Theinfluenza Replikin virus peptides comprise from 7 to about 50 aminoacids including:

[0086] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue;

[0087] (2) at least one histidine residue; and

[0088] (3) at least 6% lysine residues. (Influenza Replikin).

[0089] In another aspect of the invention, there is provided a processfor stimulating the immune system of a subject to produce antibodiesthat bind specifically to an influenza virus Replikin sequence, saidprocess comprising administering to the subject an effective amount ofdosage of a composition comprising at least one influenza virus Replikinpeptide. In a preferred embodiment the composition comprises at least onpeptide that is present in an emerging strain of influenza virus.

[0090] The present invention also provides antibodies that bindspecifically to an influenza virus Replikin, as defined herein, as wellas antibody cocktails containing a plurality of antibodies thatspecifically bind to influenza virus Replikins. In one embodiment of theinvention, there are provided compositions comprising an antibody orantibodies that specifically bind to an influenza Replikin and apharmaceutically acceptable carrier.

[0091] The present invention also provides therapeutic compositionscomprising one or more of isolated influenza virus peptides having from7 to about 50 amino acids comprising:

[0092] (1) at least one lysine residue located six to ten residues forma second lysine residue;

[0093] (2) at least one histidine residue; and

[0094] (3) at least 6% lysine residues, and a pharmaceutical acceptablecarrier.

[0095] In another aspect of the invention there is provided an antisensenucleic acid molecule complementary to an influenza virus hemagglutininReplikin mRNA sequence, said Replikin mRNA sequence denoting from 7 toabout 50 amino acids comprising:

[0096] (1) at least one lysine residue located six to ten residues froma second lysine residue;

[0097] (2) at least one histidine residue; and

[0098] (3) at least 6% lysine residues.

[0099] In yet another aspect of the invention there is provided a methodof simulating the immune system of a subject to produce antibodies toinfluenza virus comprising administering an effective amount of at leastone influenza virus Replikin peptide having from 7 to about 50 aminoacids comprising:

[0100] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue;

[0101] (2) at least one histidine residue; and

[0102] (3) at least 6% lysine residues.

[0103] In another aspect, there is provided a method of selecting aninfluenza virus peptide for inclusion in a preventive or therapeuticinfluenza virus vaccine comprising:

[0104] (1) obtaining at least one isolate of each strain of a pluralityof strains of influenza virus;

[0105] (2) analyzing the hemagglutinin amino acid sequence of the atleast one isolate of each strain of the plurality of strains ofinfluenza virus for the presence and concentration of Replikinsequences;

[0106] (3) comparing the concentration of Replikin sequences in thehemagglutinin amino acid sequence of the at least one isolate of eachstrain of the plurality of strains of influenza virus to theconcentration of Replikin sequences observed in the hemagglutinin aminoacid sequence of each of the strains at least one earlier time period toprovide the concentration of Replikins for at least two time periods,said at least one earlier time period being within about six months toabout three years prior to step (1);

[0107] (4) identifying the strain of influenza virus having the highestincrease in concentration of Replikin sequences during the at least twotime periods;

[0108] (5) selecting at least one Replikin sequence present in thestrain of influenza virus peptide identified in step (4) as a peptidefor inclusion in an influenza virus vaccine.

[0109] The present invention also provides a method of making apreventive or therapeutic influenza virus vaccine comprising:

[0110] (1) identifying a strain of influenza virus as an emergingstrain;

[0111] (2) selecting at least one Replikin sequence present in theemerging strain as a peptide template for influenza virus vaccinemanufacture,

[0112] (3) synthesizing peptides having the amino acid sequence of theat least one Replikin sequence selected in step (2), and

[0113] (4) combining a therapeutically effective amount of the peptidesof step (3) with a pharmaceutically acceptable carrier and/or adjuvant.

[0114] In another aspect, the invention is directed to a method ofidentifying an emerging strain of influenza virus for diagnostic,preventive or therapeutic purposes comprising:

[0115] (1) obtaining at least one isolate of each strain of a pluralityof strains of influenza virus;

[0116] (2) analyzing the hemagglutinin amino acid sequence of the atleast one isolate of each strain of the plurality of strains ofinfluenza virus for the presence and concentration of Replikinsequences;

[0117] (3) comparing the concentration of Replikin sequences in thehemagglutinin amino acid sequence of the at least one isolate of eachstrain of the plurality of strains of influenza virus to theconcentration of Replikin sequences observed in the hemagglutinin aminoacid sequence of each of the strains at at least one earlier time periodto provide the concentration of Replikins for at least two time periods,said at least one earlier time period being within about six months toabout three years prior to step (1); and

[0118] (4) identifying the strain of influenza virus having the highestincrease in concentration of Replikin sequences during the at least twotime periods.

[0119] In yet another aspect of the invention, there is provided apreventive or therapeutic influenza virus vaccine comprising at leastone isolated Replikin present in the hemagglutinin protein of anemerging strain of influenza virus and a pharmaceutically acceptablecarrier and/or adjuvant.

[0120] Also provided by the present invention is a method of preventingor treating influenza virus infection comprising administering to apatient in need thereof a preventive or therapeutic vaccine comprisingat least one isolated Replikin present in the hemagglutinin protein ofan emerging strain of influenza virus and a pharmaceutically acceptablecarrier and/or adjuvant.

[0121] Trypanosomes

[0122] In one aspect of the invention there are provided isolated orsynthesized trypanosome peptides containing a Replikin sequence. Thetrypanosome Replikin peptides comprise from 7 to about 50 amino acidsincluding:

[0123] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue;

[0124] (2) at least one histidine residue; and

[0125] (3) at least 6% lysine residues. (Trypanosome Replikins).

[0126] Malaria

[0127] One trypanosome disorder which has proved difficult to treat andfor which there is no effective vaccine is malaria. Malaria causes muchdeath, and physical and economic hardship in tropical regions. Malariais caused mainly by Plasmodium falciparum, which has proved to beextremely resistant to treatment and to date, a vaccine for malaria hasremained elusive. Thus there is a need for effective malaria vaccinesand methods of treating or preventing the disease. This applicationprovides the basis for such vaccines and methods of treatment andprevention. All of the methods described above for production of andtreatment with Replikin virus vaccines and Replikin influenza virusvaccines are applicable to the production of and treatment with Replikinmalaria vaccines.

[0128] In the present invention, there are provided vaccines and methodsfor preventing or treating malaria. The malaria vaccines comprise atleast one isolated Plasmodium falciparum Replikin. The present inventionalso provides methods for treating or preventing malaria comprisingadministering to a patient an effective amount of preventive ortherapeutic vaccine comprising at least one isolated Plasmodiumfalciparum Replikin.

[0129] Also provided by the present invention are antibodies, antibodycocktails and compositions that comprise antibodies that specificallybind to a Replikin or Replikins present in a malaria antigen ofPlasmodium falciparum.

[0130] Another example of a trypanosome which may be treated under thepresent invention as is the case for malaria, the Replikins of TreponemaPallidum (syphilis), can be used for detection, prevention, treatment ofsyphilis.

[0131] Bacteria

[0132] In one aspect of the invention there are provided isolated orsynthesized bacterial peptides containing a Replikin sequence (bacterialReplikins). The bacterial peptides comprise from 7 to about 50 aminoacids including:

[0133] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue;

[0134] (2) at least one histidine residue; and

[0135] (3) at least 6% lysine residues. (bacterial Replikins). U.S.application Ser. No. 10/105,232 filed Mar. 26, 2002 is incorporated byreference in its entirety, including but not limited to the bacterialsequence listing and information.

[0136] The present invention also provides methods for detecting thepresence of a contaminating bacterial organism in a body sample orenvironmental sample comprising:

[0137] (1) isolating nucleic acids from the body sample or environmentalsample;

[0138] (2) screening the nucleic acids for the presence of a Replikinstructure; and

[0139] (3) correlating the presence of a Replikin structure with thepresence of the contaminating organism.

[0140] In another aspect of the invention there is provided a processfor stimulating the immune system of a subject to produce antibodiesthat bind specifically to a bacterial Replikin sequence, said processcomprising administering to the subject an effective amount of a dosageof a composition comprising at least one bacterial Replikin peptide. Oneembodiment comprises at least one bacterial peptide that is present inan emerging strain of the bacterial organism if such new strain emerges.

[0141] The present invention also provides antibodies that bindspecifically to a bacterial Replikin, as defined herein, as well asantibody cocktails containing a plurality of antibodies thatspecifically bind to bacterial Replikins. In one embodiment of theinvention, there are provided compositions comprising an antibody orantibodies that specifically bind to a bacterial Replikin and apharmaceutically acceptable carrier.

[0142] The present invention also provides therapeutic compositionscomprising one or more of isolated bacterial peptides having from 7 toabout 50 amino acids comprising:

[0143] (1) at least one lysine residue located six to ten residues froma second lysine residue;

[0144] (2) at least one histidine residue;

[0145] (3) at least 6% lysine residues; and

[0146] (4) a pharmaceutically acceptable carrier.

[0147] In another aspect of the invention there is provided an antisensenucleic acid molecule complementary to a bacterial Replikin mRNAsequence, said Replikin mRNA sequence denoting from 7 to about 50 aminoacids comprising:

[0148] (1) at least one lysine residue located six to ten residues froma second lysine residue;

[0149] (2) at least one histidine residue; and

[0150] (3) at least 6% lysine residues.

[0151] In yet another aspect of the invention there is provided a methodof simulating the immune system of a subject to produce antibodies tobacteria comprising administering an effective amount of at least onebacterial Replikin peptide having from 7 to about 50 amino acidscomprising:

[0152] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue;

[0153] (2) at least one histidine residue; and

[0154] (3) at least 6% lysine residues.

[0155] In another aspect, there is provided a method of selecting abacterial Replikin peptide for inclusion in a preventive or therapeuticbacterial vaccine comprising:

[0156] (1) obtaining at least one isolate of each strain of a pluralityof strains of the bacteria;

[0157] (2) analyzing the amino acid sequence of the at least one isolateof each strain of the plurality of strains of the bacteria for thepresence and concentration of bacterial Replikin sequences;

[0158] (3) comparing the concentration of bacterial Replikin sequencesin the amino acid sequence of the at least one isolate of each strain ofthe plurality of strains of the bacteria to the concentration ofbacterial Replikin sequences observed in the amino acid sequence of eachof the strains at least one earlier time period to provide theconcentration of bacterial Replikins for at least two time periods, saidat least one earlier time period being within about six months to aboutthree years prior to step (1), or earlier in rapidly mutating bacteria;

[0159] (4) indentifying the strain of the bacteria having the highestincrease in concentration of bacterial Replikin sequences during the atleast two time periods; and

[0160] (5) selecting at least one bacterial Replikin sequence present inthe strain of the bacterial peptide identified in step (4) as a peptidefor inclusion in the bacterial vaccine.

[0161] The present invention also provides a method of making apreventive or therapeutic bacterial vaccine comprising:

[0162] (1) identifying a strain of a bacteria as an emerging strain;

[0163] (2) selecting at least one bacterial Replikin sequence present inthe emerging strain as a peptide template for the bacterial vaccinemanufacture;

[0164] (3) synthesizing peptides having the amino acid sequence of theat least one bacterial Replikin sequence selected in step (2); and

[0165] (4) combining a therapeutically effective amount of the peptidesof step (3) with a pharmaceutically acceptable carrier and/or adjuvant.

[0166] In another aspect, the invention is directed to a method ofidentifying an emerging strain of bacteria for diagnostic, preventive ortherapeutic purposes comprising:

[0167] (1) obtaining at least one isolate of each strain of a pluralityof strains of the bacteria;

[0168] (2) analyzing the amino acid sequence of the at least one isolateof each strain of the plurality of strains of the bacteria for thepresence and concentration of bacterial Replikin sequences;

[0169] (3) comparing the concentration of bacterial Replikin sequencesin the amino acid sequence of the at least one isolate of each strain ofthe plurality of strains of the bacteria to the concentration ofbacterial Replikin sequences observed in the amino acid sequence of eachof the strains at at least one earlier time period to provide theconcentration of bacterial Replikins for at least two time periods, saidat least one earlier time period being within about six months to aboutthree years prior to step (1); and

[0170] (4) identifying the strain of the bacteria having the highestincrease in concentration of bacterial Replikin sequences during the atleast two time periods.

[0171] In yet another aspect of the invention, there is provided apreventive or therapeutic bacterial vaccine comprising at least oneisolated bacterial Replikin present in a protein of an emerging strainof the bacteria and a pharmaceutically acceptable carrier and/oradjuvant.

[0172] Two important sub-species of bacteria, classified undermycobacteria, are Mycobacterium leprae (leprosy) whose 30-s ribosomalprotein has a C-terminal Replikin and Mycobacterium tuberculosis(tuberculosis) whose ATPase has three Replikins:

[0173] Replikin in 30s ribosomal protein s6 of Mycobacterium leprae(leprosy) is:

[0174] kvmrtdkh (SEQ ID NO. 699)

[0175] Replikins in the ATPase of Mycobacterium tuberculosis are:

[0176] hprpkvaaalkdsyrlk (SEQ ID NO. 700)

[0177] hprpkvaaalk (SEQ ID NO. 701)

[0178] ksaqkwpdkflagaaqvah (SEQ ID NO. 702)

[0179] Replikins in the B-D-galactosidase of E. coli:

[0180] hawqhqgktlfisrk (SEQ ID NO. 703)

[0181] hqgktlfisrk(SEQ ID NO. 704)

[0182] Replikins in Agrobacterium tumefaciens:

[0183] hsdqqlavmiaakrlddyk (SEQ ID NO. 705)

[0184] hlldhpasvgqldlramlaveevkidnpvymek (SEQ ID NO. 706)

[0185] hpasvgqldlramlaveevkidnpvymek (SEQ ID NO. 707)

[0186] kcvmakncnikcpaglttnqeafngdpralaqylmniah (SEQ ID NO. 708)

[0187] kncnikcpaglttnqeafngdpralaqylmniah (SEQ ID NO. 709)

[0188] hhdtysiedlaqlihdakaarvrvivk (SEQ ID NO. 710)

[0189] hdtysiedlaqlihdakaarvrvivk (SEQ ID NO. 711)

[0190] hdakaarvrvivk (SEQ ID NO. 712)

[0191] kigqgakpgeggqlpspkvtveiaaarggtpgvelvsppphh (SEQ ID NO. 713)

[0192] kigqgakpgeggqlpspkvtveiaaarggtpgvelvsppph (SEQ ID NO. 714)

[0193] kaseitktlasgamshgalvaaaheavahgtnmvggmsnsgeggeh (SEQ ID NO. 715)

[0194] kaseitktlasgamshgalvaaaheavah (SEQ ID NO. 716)

[0195] kaseitktlasgamshgalvaaah (SEQ ID NO. 717)

[0196] kaseitktlasgamsh(SEQ ID NO. 718)

[0197] kryfpnvktpvggvtfaviaqavadwh (SEQ ID NO. 719)

[0198] hhiaaglgfgasavyplgvqfraeekfgadadkafkrfakaaekslmk (SEQ ID NO. 720)

[0199] hhiaaglgfgasavyplgvqfraeekfgadadkafkrfakaaekslmk (SEQ ID NO. 721)

[0200] hhiaaglgfgasavyplgvqfraeekfgadadkafkrfakaaek (SEQ ID NO. 722)

[0201] hhiaaglgfgasavyplgvqfraeekfgadadkafkrfak (SEQ ID NO. 723)

[0202] hhiaaglgfgasavyplgvqfraeekfgadadk (SEQ ID NO. 724)

[0203] hiaaglgfgasavyplgvqfraeekfgadadkafkrfakaaekslmk (SEQ ID NO. 725)

[0204] hiaaglgfgasavyplgvqfraeekfgadadkafkrfakaaek (SEQ ID NO. 726)

[0205] hiaaglgfgasavyplgvqfraeekfgadadkafkrfak (SEQ ID NO. 727)

[0206] hiaaglgfgasavyplgvqfraeekfgadadk (SEQ ID NO. 728)

[0207] kfglydaafeksscgvgfitrkdgvqth (SEQ ID NO. 729)

[0208] Also provided by the present invention is a method of preventingor treating a bacterial infection comprising administering to a patientin need thereof a preventive or therapeutic vaccine comprising at leastone isolated bacterial Replikin present in a protein of an emergingstrain of the bacteria and a pharmaceutically acceptable carrier and/oradjuvant.

[0209] Fungus

[0210] In one aspect of the invention there are provided isolated orsynthesized fungal peptides containing a Replikin sequence. The fungalReplikin peptides comprise from 7 to about 50 amino acids including:

[0211] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue;

[0212] (2) at least one histidine residue; and

[0213] (3) at least 6% lysine residues (fungal Replikins).

[0214] All of the methods described above for production of andtreatment with bacterial Replikin vaccines are applicable to theproduction of and treatment with fungal Replikin vaccines.

[0215] In another aspect of the invention there is provided a processfor stimulating the immune system of a subject to produce antibodiesthat bind specifically to a fungal Replikin sequence, said processcomprising administering to the subject an effective amount of a dosageof a composition comprising at least one fungal Replikin peptide.

[0216] The present invention also provides antibodies that bindspecifically to a fungal Replikin, as defined herein, as well asantibody cocktails containing a plurality of antibodies thatspecifically bind to viral Replikins. In one embodiment of theinvention, there are provided compositions comprising an antibody orantibodies that specifically bind to a fungal Replikin and apharmaceutically acceptable carrier.

[0217] The present invention also provides therapeutic compositionscomprising one or more of isolated fungal peptides having from 7 toabout 50 amino acids comprising:

[0218] (1) at least one lysine residue located six to ten residues froma second lysine residue;

[0219] (2) at least one histidine residue;

[0220] (3) at least 6% lysine residues; and

[0221] (4) a pharmaceutically acceptable carrier.

[0222] In another aspect of the invention there is provided an antisensenucleic acid molecule complementary to an fungal Replikin mRNA sequence,said Replikin mRNA sequence having from 7 to about 50 amino acidscomprising:

[0223] (1) at least one lysine residue located six to ten residues froma second lysine residue;

[0224] (2) at least one histidine residue; and

[0225] (3) at least 6% lysine residues.

[0226] In another aspect of the invention there is provided a processfor stimulating the immune system of a subject to produce antibodiesthat bind specifically to a fungal Replikin sequence, said processcomprising administering to the subject an effective amount of a dosageof a composition comprising at least one Replikin peptide.

[0227] Increasing Replication

[0228] In yet another aspect of the invention there is provided a methodfor increasing the replication rate of an organism comprisingtransforming a gene encoding an enzyme or other protein having areplication function in the organism with at least one Replikinstructure.

[0229] Definitions

[0230] As used herein, the term “peptide” or “protein” refers to acompound of two or more amino acids in which the carboxyl group of oneis united with an amino group of another, forming a peptide bond. Theterm peptide is also used to denote the amino acid sequence encodingsuch a compound. As used herein, “isolated” or “synthesized” peptide orbiologically active portion thereof refers to a peptide that issubstantially free of cellular material or other contaminating peptidesfrom the cell or tissue source from which the peptide is derived, orsubstantially free from chemical precursors or other chemicals whenchemically synthesized by any method, or substantially free fromcontaminating peptides when syntehsized by recombinant gene techniques.

[0231] As used herein, a Replikin peptide or Replikin protein is anamino acid sequence having 7 to about 50 amino acids comprising:

[0232] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue;

[0233] (2) at least one histidine residue;

[0234] (3) at least 6% lysine residues.

[0235] Similarly, a Replikin sequence is the amino acid sequenceencoding such a peptide or protein.

[0236] As used herein, “emerging strain” as used herein refers to astrain of a virus, bacterium, fungus, or other organisms identified ashaving an increased increasing concentration of Replikin sequences inone or more of its protein sequences relative to the concentration ofReplikins in other strains of such organism. The increase or increasingconcentration of Replikins occurs over a period of at least about sixmonths, and preferably over a period of at least about one year, mostpreferably over a period of at least about three years or more, forexample, in influenza virus, but may be a much shorter period of timefor bateria and other organisms.

[0237] As used herein, “mutation” refers to change in this structure andproperties of an organism caused by substitution of amino acids. Incontrast, the term “conservation” as used herein, refers to conservationof particular amino acids due to lack of substitution.

BRIEF DESCRIPTION OF THE DRAWINGS

[0238]FIG. 1 is a bar graph depicting the frequency of occurrence ofReplikins in various organisms.

[0239]FIG. 2 is a graph depicting the percentage of malignin permilligram total membrane protein during anaerobic replication ofglioblastoma cells.

[0240]FIG. 3 is a bar graph showing amount of antimalignin antibodyproduced in response to exposure to the recognin 16-mer.

[0241]FIG. 4A is a photograph of a blood smear taken with ordinary andfluorescent light. FIG. 4B is a photograph of a blood smear taken withordinary and fluorescent light illustrating the presence of two leukemiccells. FIG. 4C is a photograph of a dense layer of glioma cells in thepresence of antimalignin antibody. FIG. 4D and FIG. 4E are photographsof the layer of cells in FIG. 4C taken at 30 and 45 minutes followingaddition of antimalignin antibody

[0242]FIG. 4F is a bar graph showing the inhibition of growth of smallcell lung carcinoma cells in vitro by antimalignin antibody.

[0243]FIG. 5 is a plot of the amount of antimalignin antibody present inthe serum of patients with benign or malignant breast disease pre-andpost surgery.

[0244]FIG. 6 is a box diagram depicting an embodiment of the inventionwherein a computer is used to carry out the 3-point-recognition methodof identifying Replikin sequences.

[0245]FIG. 7 is a graph showing the concentration of Replikins observedin hemagglutinin of influenza B and influenza A strain, H1N1, on a yearby year basis from 1918 through 2001.

[0246]FIG. 8 is a graph of the Replikin concentration observed inhemagglutinin of influenza A strains, H2N2 and H3N2, as well as anemerging strain defined by its constituent Replikins, designatedH3N2(R), on a year by year basis from 1950 to 2001.

DETAILED DESCRIPTION OF THE INVENTION

[0247] The identification of a new family of small peptides related tothe phenomenon of rapid replication, referred to herein as Replikins,provides targets for detection of pathogens in a sample and developingtherapies, including vaccine development. In general, knowledge of andidentification of this family of peptides enables development ofeffective therapies and vaccines for any organism that harborsReplikins. Identification of this family of peptides also provides forthe detection of viruses and virus vaccine development.

[0248] For example, identification of this family of peptides providesfor the detection of influenza virus and provides new targets forinfluenza treatment. Identification of this family of peptides alsoprovides for example, for the detection of malaria and provides newtargets for malaria vaccine development. Further examples provided bythe identification of this family of peptides include the detection ofinfectious disease Replikins, cancer immune Replikins and structuralprotein Replikins.

[0249] Rapid replication is characteristic of virulence in certainbacteria, viruses and malignancies, but no chemistry common to rapidreplication in different organisms has been described. We have found afamily of conserved small protein sequences related to rapidreplication, which we have named Replikins. Such Replikins offer newtargets for developing effective detection methods and therapies. Thefirst Replikin found was the glioma Replikin, which was identified inbrain glioblastoma multiforme (glioma) cell protein called malignin.

[0250] Hydrolysis and mass spectrometry of malignin revealed the novel16 mer peptide sequence which contains the glioma Replikin. ThisReplikin was not found in databases for the normal healthy human genomeand therefore appeared to be derived from some source outside the body.

[0251] We have devised an algorithm to search for the glioma Replikin orhomologue thereof. Homologues were not common in over 4,000 proteinsequences, but were found, surprisingly, in all tumor viruses, and inthe replicating proteins of algae, plants, fungi, viruses and bacteria.

[0252] We have identified that both 1) Replikin concentration (number ofReplikins per 100 amino acids) and 2) Replikin composition correlatewith the functional phenomenon of rapid replication. These relationshipsprovide functional basis for the determination that Replikins arerelated quantitatively as well as qualitatively to the rate ofreplication.

[0253] The first functional basis for Replikins role to rapidreplication is seen in glioma replication. The fact that glioma maligninis enriched ten-fold compared to the five-fold increase in cell numberand membrane protein concentration in rapid replication of glioma cellssuggests an integral relationship of the Replikins to replication. Whenthe glioma Replikin was synthesized in vitro and administered as asynthetic vaccine to rabbits, abundant antimalignin antibody wasproduced. This establishes the antigenic basis of the antimaligninantibody in serum (AMAS) test, and provides the first potentialsynthetic cancer vaccine and the prototype for Replikin vaccines inother organisms. With the demonstration of this natural immunerelationship of the Replikins to replication and this natural immuneresponse to cancer Replikins, which overrides cell type, based upon theshared specificity of cancer Replikins and rapid replication, bothpassive augmentation of this immunity with antimalignin antibody andactive augmentation with synthetic Replikin vaccines now is possible.

[0254] The relationship between the presence of antimalignin antibodyand survival in patients was shown in a study of 8,090 serum specimensfrom cancer patients. The study showed that the concentration ofantimalignin antibody increases with age, as the incidence of cancer inthe population increases, and increases further two to three-fold inearly malignancy, regardless of cell type. In vitro, the antimaligninantibody is cytotoxic to cancer cells at picograms (femtomoles) percancer cell, and in vivo the concentration of antimalignin antibodyrelates quantitatively to the survival of cancer patients. As shown inglioma cells, the stage in cancer at which cells have only beentransformed to the immortal malignant state but remain quiescent ordormant, now can be distinguished from the more active life-threateningreplicating state, which is characterized by the increased concentrationof Replikins. In addition, clues to the viral pathogenesis of cancer maybe found in the fact that glioma glycoprotein 10B has a 50% reduction incarbohydrate residues when compared to the normal 10B. This reduction isassociated with virus entry in other instances, and so may be evidenceof the attachment of virus for the delivery of virus Replikins to the 1OB of glial cells as a step in the transformation to the malignantstate.

[0255] Our study concerning influenza virus hemagglutinin proteinsequences and influenza epidemiology over the past 100 years, hasprovided a second functional basis for the relations of Replikins torapid replication. Only serological hemagglutinin and antibodyclassification, but no strain-specific conserved peptide sequences havepreviously been described in influenza. Further, no changes inconcentration and composition of any strain-specific peptide sequenceshave been described previously that correlate with epidemiologicallydocumented epidemics or rapid replication. In this study, a four toten-fold increase in the concentration of strain-specific influenzaReplikins in one of each of the four major strains, influenza B,(A)H1N1, (A)H2N2 and (A)143N2, is shown to relate to influenza epidemicscaused by each strain from 1902 to 2001.

[0256] We then showed that these increases in concentration are due tothe reappearance of at least one specific Replikin composition from 1 toup to 64 years after its disappearance, plus the emergence of newstrain-specific Replikin compositions. Previously, no strain-specificchemical structures were known with which to predict the strains thatwould predominate in coming influenza seasons, nor to devise annualmixtures of whole-virus strains for vaccines. The recent sharp increasein H3N2 Replikin concentration (1997 to 2000), the largest in H3N2'shistory, and the reappearance of specific Replikin compositions thatwere last seen in the high mortality H3N2 pandemic of 1968, and in thetwo high mortality epidemics of 1975 and 1977, but were absent for 20-25years, together may be a warning of coming epidemics. This high degreeof conservation of Replikin structures observed, whereby the identicalstructure can persist for 100 years, or reappear after an absence offrom one to 64 years, indicate that what was previously thought to bechange due to random substitution of amino acids in influenza proteinsis more likely to be change due to an organized process of conservationof Replikins.

[0257] The conservation of Replikins is not unique to influenza virusbut was also observed in other sources, for example in foot and mouthdisease virus, type 0, HIV tat, and wheat.

[0258] A third functional basis for Replikins' role in rapid replicationis seen in the increase in rapid replication in HIV. Replikinconcentration was shown to be related to rapid replication in HIV. Wefound the Replikin concentration in the slow growing low-titre strain ofHIV (NS 1, “Bru”), which is prevalent in early stage infection, to beone-sixth of the Replikin concentration in the rapidly-growinghigh-titre strain of HIV (SI, “Lai”)(prevalent in late stage HIVinfection).

[0259] Further examples demonstrate the relationship of Replikins torapid replication. In the “replicating protein,” of tomato curl leafgemini virus which devastates tomato crops, the first 161 amino acids,the sequence which has been shown to bind to DNA, was shown to containfive Replikins. In malaria, legendary for rapid replication whentrypanosomes are released from the liver in the tens of thousands fromone trypanosome, multiple, novel, almost ‘flamboyant’ Replikinstructures have been found with concentrations of up to 36 overlappingReplikins per 100 amino acids.

[0260] The conservation of any structure is critical to whether thatstructure provides a stable invariant target to attack and destroy or tostimulate. When a structure is tied in some way to a basic survivalmechanism of the organism, the structures tend to be conserved. Avarying structure provides an inconstant target, which is a goodstrategy for avoiding attackers, such as antibodies that have beengenerated specifically against the prior structure and thus areineffective against the modified form. This strategy is used byinfluenza virus, for example, so that a previous vaccine may be quiteineffective against the current virulent virus.

[0261] Replikins as Stable Targets for Treatment

[0262] Both bacteria and HIV have both Replikin and non-Replikin aminoacids. In HIV, for example, there has been a recent increase indrug-resistance from 9% to 13% due to mutation, that is substitution ofnon-Replikin amino acids. (See detailed analysis of TAT protein of HIVdiscussed herein). In bacteria, the development of ‘resistant strains’is due to a similar mechanism. However, we have found that Replikinstructures do not mutate or change to the same degree as non Replikinamino acids (see also discussion of foot and mouth disease virusconservation of Replikins discussed herein). The Replikin structures, asopposed to the non-Replikin structures are conserved and thus providenew constant targets for treatment.

[0263] Certain structures too closely related to survival functionsapparently cannot change constantly. Because an essential component ofthe Replikin structure is histidine (h), which is know for its frequentbinding to metal groups in redox enzymes and probable source of energyneeded for replication, and since this histidine structure remainsconstant, this structure remains all the more attractive a target fordestruction or stimulation.

[0264] From a proteomic point of view, inventors construction of atemplate based on the newly determined glioma peptide sequence led themto the discovery of a wide class of proteins with related conservedstructures and a particular function, in this case replication. Examplesof the increase in Replikin concentration with virulence of a diseaseinclude, influenza, HIV, cancer and tomato leaf curl virus. This newlyrecognized class of structures is related to the phenomenon of rapidreplication in organisms as diverse as yeast, algae, plants, the geminicurl leaf tomato virus, HIV and cancer.

[0265] Replikin concentration and composition provide new quantitativemethods to detect and control the process of replication, which iscentral to the survival and dominance of each biological population. Thesharing of immunological specificity by diverse members of the class, asdemonstrated with antimalignin antibody for the glioma and relatedcancer Replikins, suggests that B cells and their product antibodies mayrecognize Replikins by means of a similar recognition language.

[0266] Examples of peptide sequences of cancer Replikins or ascontaining a Replikin, i.e., a homologue of the glioma peptide,kagvaflhkk, may be found in such cancers of, but not limited to, thelung, brain, liver, soft-tissue, salivary gland, nasopharynx, esophagus,stomach, colon, rectum, gallbladder, breast, prostate, uterus, cervix,bladder, eye, forms of melanoma, lymphoma, leukemia, and kidney.

[0267] Replikins provide for: 1) detection of pathogens by qualitativeand quantitative determinations of Replikins; 2) treatment and controlof a broad range of diseases in which rapid replication is a key factorby targeting native Replikins and by using synthetic Replikins asvaccines; and 3) fostering increased growth rates of algal and plantfoods.

[0268] The first Replikin sequence to be identified was the cancer cellReplikin found in a brain cancer protein, malignin, which wasdemonstrated to be enriched ten-fold during rapid anaerobic replicationof glioblastoma multiforme (glioma) cells. (FIG. 2) Malignin is a 10 KDaportion of the 250 KDa glycoprotein 10B, which was isolated in vivo andin vitro from membranes of glioblastoma multiforme (glioma) cells.Hydrolysis and mass spectroscopy of malignin revealed a 16-mer peptidesequence, ykagvaflhkkndide (SEQ ID NO.:4), which is referred to hereinas the glioma Replikin and which includes the shorter peptide,kagvaflhkk (SEQ ID NO.: 1), both of which apparently are absent in thenormal human genome.

[0269] When the 16-mer glioma Replikin was synthesized and injected as asynthetic vaccine into rabbits, abundant antimalignin antibody wasproduced. (Bogoch et al., Cancer Detection and Prevention, 26 (Suppl.1): 402 (2002)). The concentration of antimalignin antibody in serum invivo has been shown to relate quantitatively to the survival of cancerpatients. (Bogoch et al., Protides of Biological Fluids, 31:739-747(1984). In vitro antimalignin antibodies have been shown to be cytotoxicto cancer cells at a concentration of picograms (femtomolar) per cancercell. (Bogoch et al., Cancer Detection and Prevention, 26 (Suppl. 1):402 (2002).

[0270] Studies carried out by the inventors showed that the gliomaReplikin is not represented in the normal healthy human genome.Consequently, a search for the origin and possible homologues of theReplikin sequence was undertaken by analysis of published sequences ofvarious organisms.

[0271] By using the 16-mer glioma Replikin sequence as a template andconstructing a recognition proteomic system to visually scan the aminoacid sequences of proteins of several different organisms, a new classof peptides, the Replikins, was identified. The present inventionprovides a method for identifying nucleotide or amino acid sequencesthat include a Replikin sequence. The method is referred to herein as a3-point-recognition method. The three point recognition methodcomprises: a peptide from 7 to about 50 amino acids including:

[0272] (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue;

[0273] (2) at least one histidine residue; and

[0274] (3) at least 6% lysine residues. (Replikin).

[0275] These peptides or proteins constitute a new class of peptides inspecies including algae, yeast, fungi, amoebae, bacteria, plant, virusand cancer proteins having replication, transformation, or redoxfunctions. Replikin peptides have been found to be concentrated inlarger ‘replicating’ and ‘transforming’ proteins (so designated by theirinvestigators, See Table 2) and cancer cell proteins. No sequences werefound to be identical to the malignin 16-mer peptide. TABLE 2 Examplesof Replikins in various organisms - prototype: Glioma Replikin*kagvaflhkk (SEQ ID No.: 1) SEQ ID NO. Algae: 34 Caldophera proliferakaskftkh 35 Isolepisprolifera kaqaetgeikgh Yeast: 36 Schizosaccharomycespombe ksfkypkkhk 37 Oryza sativa kkaygnelhk 2 Sacch. cerevisiaereplication binding protein hsikrelgiifdk Fungi: 38 Isocitrate lyase ICI1, Penicillium marneffei kvdivthqk 39 DNA-dependent RNA polymerase 11,Diseula destructiva kleedaayhrkk 40 Ophiostoma novo-u1m 1, RNA in Dutchelm disease kvilplrgnikgiffkh fungus Amoeba: 41 Entamoeba invadens,histone H2B klilkgdlnkh Bacteria: 42 Pribosomal protein replicationfactor, Helicobacter pylori ksvhaflk 10 Replication-associated proteinStaph. Aureus 43 Mycoplasma pulmonic, chromosome replication kkektthnk90 Macrophage infectivity potentiator, L. legionella kvhffqlkk Plants:44 Arabidopsis thaliana, prolifera kdhdfdgdk 45 Arabidopsis thaliana,cytoplasmic ribosomal kmkglkqkkah 46 Arabidopsis thaliana, DNA bindingprotein kelssttqeksh Viruses: 9 Replication associated protein A [Maizestreak virus] Kekkpskdeimrdiish 11 Bovine herpes virus 4, DNAreplication protein hkinitngqk 12 Meleagrid herpesvirus 1, replicationbinding protein hkdlyrllmk 47 Feline immunodeficiency hlkdyklvk 3 Footand Mouth Disease (O) hkqkivapvk 5 HIV Type 1 kcfncgkegh 7 HIV Type 2kcwncgkegh Tumor 48 Rous sarcoma virus tyrosine-protein kinase kklrhekViruses: 49 v-yes, avian sarcoma kklrhdk 50 c-yes, colon cancer,malignant melanoma kklrhdk 51 v-srcC, avian sarcoma kklrhek 52 c-src,colon, mammary, panrcreatic cancer kklrhek 53 Neuroblastoma RAS viral(v-ras) oncogene kqahelak 54 VPl (major capsid protein) [Polyamavirussp.] kthrfskh 55 Sindbis knlhekik 56 El [Human papilloamavirus type 71]khrpllqlk 57 v-erbB from AEV and c-erb kspnhvk 58 v-fms (feline sarcoma)knihlekk 59 c-fms (acute and chronic myelomonocytic tumors) knihlekk 60large t-antigen I [Polyomavirus sp.l kphlaqslek 61 middle t-antigen[Polyomavirus sp,l- kqhrelkdk 62 small t-antigen [Polyomavirus spJ,kqhrelkdk 63 v-abl, murine acute leukemia kvpvlisptlkh 64 Human T-celllymphotropic virus typo 2 kslllevdkdish 65 c-kit, GI tumors, small celllung carcinoma kagitimvkreyh 18 Hepatitis C hyppkpgcivpak Trans- 66Transforming protein myb Ksgkhlgk Forming 67 Transforming protein myc,Burkitt lymphoma krreqlkhk Proteins: 68 Ras-related GTP-binding proteinksfevikvih 69 Transforming protein ras (teratocarcinoma) kkkhtvkk 70TRAF-associated NF•kB activator TANK kaqkdhlsk 71 RFP transformingprotein hlkrvkdlkk 72 Transforming protein D (S.C.) kygspkhrlik 73Papilloma virus type 11, transforming protein klkhilgkarfik 74 Proteintryosine kinasc (EC 2.7.1.ll2slk kgdhvkhykirk 75 Transforming protein(ax1(−)) keklrdvmvdrhk 76 Transforming protein (N-myc) klqarqqqllkkieh77 Fibroblast growth factor 4 (Kaposi sarcoma) kkgnrvsptmkvth Cancer 78Matrix metaloproteinase 7 (uterine) keiplhfrk Cell 79 Transcriptionfactor 7-like kkkphikk Proteins: 80 Breast cancer antigen NY-BR-87ktrhdplak 81 BRCA-1-Associated Ring Domain Protein (breast) khhpkdnlik82 {grave over ( )}Autoantigen from a breast tumor′ khkrkkfrqk 83 GliomaReplikin (this study) kagvaflhkk 84 Ovarian cancer antigen khkrkkfrqk 85EE L leukemia kkkskkhkdk 86 Proto-oncogene tyrosine-protein kinaseC-ABLE hksekpalprk 87 Adenomatosis polyposis coli kkkkpsrlkgdnek 88Gastric cancer transforming protein ktkkgnrvsptmkvth 89 Transformingprotein (K-RAS 2B), lung khkekmskdgkkkkkksk

[0276] Identification of an amino acid sequence as a Replikin or ascontaining a Replikin, i.e., a homologue of the glioma peptide,kagvaflhkk, requires that the three following requirements be met.According to the three point recognition system the sequences have threeelements: (1) at least one lysine residue located six to ten residuesfrom another lysine residue; (2) at least one histidine residue; and (3)a composition of at least 6% lysine within an amino acid sequence of 7to about 50 residues.

[0277] Databases were searched using the National Library of Medicinekeyword “PubMed” descriptor for protein sequences containing Replikinsequences. Over 4,000 protein sequences were visually examined forhomologues. Sequences of all individual proteins within each group ofPubMed-classified proteins were visually scanned for peptides meetingthe three above-listed requirements. An infrequent occurrence ofhomologues was observed in “virus peptides” as a whole (1.5%) (N=953),and in other peptides not designated as associated with malignanttransformation or replication such as “brain peptides” and“neuropeptides” (together 8.5%) (N=845). However, surprisingly,homologues were significantly more frequently identified in large“replicating proteins,” which were identified as having an establishedfunction in replication in bacteria, algae, and viruses. Even moresurprising was the finding that Replikin homologues occurred in 100% of“tumor viruses” (N=250), in 97% of “cancer proteins” (N=401), and in 85%of “transforming viruses” (N=248). These results suggest that there areshared properties of cancer pathogenesis regardless of cell type andsuggest a role of viruses in carcinogenesis, i.e., conversion of cellsfrom a transformed albeit dormant state to a more virulent activelyreplicating state.

[0278] Homologues of the following amino acid sequence, kagvaflhkk, asdefined by the three point recognition method, were found in suchviruses, or viral peptides, as, but not limited to, adenovirus,lentivirus, a-virus, retrovirus, andeno-associated virus, humanimmunodeficiency virus, hepatitis virus, influenza virus, maize streakvirus, herpes virus, bovine herpes virus, feline immunodeficiency virus,foot and mouth disease virus, small pox virus, rous sarcoma virus,neuroblastoma RAS viral oncogene, polyamavirus, sindbis, human papillomavirus, myelomonocytic tumor virus, murine acute leukemia, T-celllymphotropic virus, and tomato leaf curl virus.

[0279] Replikins are present in such bacteria as, but not limited to,Acetobacter, Achromobacter, Actinomyces, Aerobacter, Alcaligenes,Arthrobacter, Azotobacter, Bacillus, Brevibacterium, Chainia,Clostridium, Corynebacterium, Erwinia, Escheria, Lebsiella,Lactobacillus, Haemophilus, Flavobacterium, Methylomonas, Micrococcus,Mycobacterium, Micronomspora, Mycoplasma, Neisseria, Nocardia, Proteus,Pseudomonas, Rhizobium, Salmonella, Serratia, Staphylococcus,Streptocossus, Streptomyces, Streptosporangium, Streptovirticillium,Vibrio, peptide, and Xanthomas.

[0280] Replikins are present in such fungi as, but not limited to,Penicillium, Diseula, Ophiostoma novo-ulim, Mycophycophta, Phytophthorainfestans, Absidia, Aspergillus, Candida, Cephalosporium, Fusarium,Hansenula, Mucor, Paecilomyces, Pichia, Rhizopus, Torulopsis,Trichoderma, and Erysiphe.

[0281] Replikins are present in such yeast as, but not limited to,Saccharomyces, Cryptococcus, including Cryptococcus neoformas,Schizosaccharomyces, and Oryza.

[0282] Replikins are present in algae such as, but not limited to,Caldophera, Isolepisprolifera, Chondrus, Gracilaria, Gelidium, Caulerpa,Laurencia, Cladophexa, Sargassum, Penicillos, Halimeda, Laminaria,Fucus, Ascophyllum, Undari, Rhodymenia, Macrocystis, Eucheuma,Ahnfeltia, and Pteroclasia.

[0283] Replikins are present in amoeba such as, but not limited to,Entamoeba (including Entamoeba invadens), Amoebidae, Acanthamoeba andNaegleria.

[0284] Replikins are present in plants such as, but not limited to,Arabidopsis, wheat, rice, and maize.

Auxiliary Specifications

[0285] To permit classification of subtypes of Replikins, additional or“auxiliary specifications” to the basic “3-point-recognition”requirements may be added: (a) on a structural basis, such as the commonoccurrence of adjacent di- and polylysines in cancer cell proteins(e.g., transforming protein P21B(K-RAS 2B), lung, Table 2, SEQ ID NO.:89), and other adjacent di-amino acids in TOLL-like receptors, or b) ona functional basis, such as exhibiting ATPase, tyrosine kinase or redoxactivity as seen in Table 2.

Functional Derivatives

[0286] “Functional derivatives” of the Replikins as described herein arefragments, variants, analogs, or chemical derivatives of the Replikins,which retain at least a portion of the immunological cross reactivitywith an antibody specific for the Replikin. A fragment of the Replikinpeptide refers to any subset of the molecule. Variant peptides may bemade by direct chemical synthesis, for example, using methods well knownin the art. An analog of a Replikin to a non-natural proteinsubstantially similar to either the entire protein or a fragmentthereof. Chemical derivatives of a Replikin contain additional chemicalmoieties not normally a part of the peptide or peptide fragment.

[0287] As seen in FIG. 2, during anaerobic respiration when the rate ofcell replication is increased, malignin is enriched. That is, maligninis found to increase not simply in proportion to the increase in cellnumber and total membrane proteins, but is enriched as much as ten-foldin concentration, starting with 3% at rest and reaching 30% of totalmembrane protein. This clear demonstration of a marked increase inReplikin concentration with glioma cell replication points to, and isconsistent with, the presence of Replikins identified with the 3-pointrecognition method in various organisms. For example, Replikins wereidentified in such proteins as “Saccharomyces cerevisiae replicationbinding protein” (SEQ ID NO.: 2) (hsikrelgiifdk); the “replicationassociated protein A of maize streak virus” (SEQ ID NO.: 8)(kyivcareahk) and (SEQ ID NO.: 9) (kekkpskdeimrdiish); the“replication-associated protein of Staphylococcus aureus ” (SEQ ID NO.:10) (kkektthnk); the “DNA replication protein of bovine herpes virus 4”(SEQ ID NO.: 11) (hkinitngqk); and the “Mealigrid herpes virus 1replication binding protein” (SEQ ID NO.: 12) (hkdlyrllmk). Previousstudies of tomato leaf curl gemini virus show that the regulation ofvirus accumulation appears to involve binding of amino acids 1-160 ofthe “replicating protein” of that virus to leaf DNA and to otherreplication protein molecules during virus replication. Analysis of thissequence showed that amino acids 1-163 of this “replicating protein”contain five Replikins, namely: (SEQ ID NO.: 13) kfrinaknyfltyph, (SEQID NO.: 14) knletpvnklfiricrefh, (SEQ ID NO.: 15) hpniqaaksstdvk, (SEQID NO.: 16) ksstdvkaymdkdgdvldh, and (SEQ ID NO.: 17)kasalnilrekapkdfvlqfh.

[0288] Table 2 shows that Replikin-containing proteins also areassociated frequently with redox functions, and protein synthesis orelongation, as well as with cell replication. The association withmetal-based redox functions, the enrichment of the Replikin-containingglioma malignin concentration during anaerobic replication, and thecytotoxicity of antimalignin at low concentrations (picograms/cell)(FIGS. 4c-f), all suggest that the Replikins are related to centralrespiratory survival functions, have been found less often subjected tothe mutations characteristic of non-Replikin amino acids.

[0289] Of particular interest, it was observed that at least oneReplikin per 100 amino acids was found to be present in thehemagglutinin proteins of almost all of the individual strains ofinfluenza viruses examined. The Replikin sequences that were observed tooccur in the hemagglutinin proteins of isolates of each of the fourprevalent strains of influenza virus, influenza B, H1N1, H2N2, and H3N2,for each year that amino acid sequence data are available (1902-2001),are shown in Tables 3, 4, 5 and 6, below. TABLE 3 Replikin Sequencespresent in hemagglutinins of Influenza B viruses in each year for whichamino acid sequences were available (1902-2001). Influenza B ReplikinsYear Detected in Influenza B strain (Peak in FIG. 7: EB1   EB2) kshfanlk(SEQ ID NO. 91) 1902, 19, 24, 38, 40, 43, 51, 59, 75, 76, 77, 89, 90,93, 97, 98, 99, 00, 01 kshfanlkgtk (SEQ ID NO. 92) 1902, 19, 24, 38, 40,43, 51, 59, 75, 76, 77, 89, 90, 93, 97, 98, 99, 00, 01kshfanlkgtktrgklcpk (SEQ ID NO. 93) 1902, 19, 24, 38, 40, 43, 51, 59,75, 76, 77, 89, 90, 93, 97, 98, 99, 00, 01 hekygglnk (SEQ ID NO. 94)1902, 19, 24, 38, 40, 43, 51, 59, 75, 76, 77, 89, 90, 93, 97, 98, 99,00, 01 hekygglnksk (SEQ ID NO. 95) 1902, 19, 24, 38, 40, 43, 51, 59, 75,76, 77, 89, 90, 93, 97, 98, 99, 00, 01 hekygglnkskpyytgehak (SEQ ID NO.96) 1902, 19, 24, 38, 40, 43, 51, 59, 75, 76, 77, 89, 90, 93, 97, 98,99, 00, 01 hakaigncpiwvk (SEQ ID NO. 97) 1902, 19, 24, 38, 40, 43, 51,59, 75, 76, 77, 89, 90, 93, 97, 98, 99, 00, 01 hakaigncpiwvktplklangtk(SEQ ID NO. 98) 1902, 19, 24, 38, 40, 43, 51, 59, 75, 76, 77, 89, 90,93, 97, 98, 99, 00, 01 hakaigncpiwvktplklangtkyrppak (SEQ ID NO. 99)1902, 19, 24, 38, 40, 43, 51, 59, 75, 76, 77, 89, 90, 93, 97, 98, 99,00, 01 hakaigncpiwvktplklangtkyrppakllk (SEQ ID NO. 100) 1902, 19, 24,38, 40, 43, 51, 59, 75, 76, 77, 89, 90, 93, 97, 98, 99, 00, 01hfanlkgtktrgk (SEQ ID NO. 101) 1919, 76, 89, 90, 99, 00, 01hfanlkgtktrgklcpk (SEQ ID NO. 102) 1919, 76, 90, 00, 01 hsdneiqmvklygdsk(SEQ ID NO. 103) 1919 hsdneiqdkmvklygdskpqk (SEQ ID NO. 104) 1919hsdneiqmvklygdskpqk (SEQ ID NO. 105) 1919, 24, 97, 98, 00 k(a/v)silhevk(SEQ ID NO. 106) 1919, 40, 59, 90, 93 kctgtipsakasilh (SEQ ID NO. 107)1919, 00 kctgtipsakasilhevk (SEQ ID NO. 108) 1919, 93, kygglnkskpyytgeh(SEQ ID NO. 109) 1919 kvwcasgrskvikgslpligeadclh (SEQ ID NO. 110) 1919,38, 40, 43, 59, 75, 76, 77, 89, 90, 98, 99, 00 kpyytgehak (SEQ ID NO.111) 1919, 38, 40, 59, 89, 90, 93, 97, 98, 01 kcmgtipsakasilhevk (SEQ IDNO. 112) 1924, 43, 75, 76, 77, 93 hnvinaekapggpyk (SEQ ID NO. 113) 1938,93, 97, 00 hsdnetqmaklygdsk (SEQ ID NO. 114) 1938, 93, 97, 00hgvavaadlkstqeaink (SEQ ID NO. 115) 1940, 59, 00hgvavaadlkstqeainkdtistqeaink (SEQ ID NO. 116) 1940klygdskpqkftssangvtth (SEQ ID NO. 117) 1943, 75, 76, 77, 93, 97, 00hsdnetqmaklygdskpqk (SEQ ID NO. 118) 1943, 75, 76, 77, 93 hfanlkgtqtrgk(SEQ ID NO. 119) 1959 kprsalkckgfh (SEQ ID NO. 120) 1988kskpyytgehakai(g/a)ncpiwvk (SEQ ID NO. 121) 2000

[0290] TABLE 4 H1N1 Replikin Sequences present in H1N1 hemagglutinins ofInfluenza viruses in each year for which amino acid sequences wereavailable (1918-2000) H1N1 Replikin Year Detected in Influenza H1N1Strain Peak in FIG. 7: P1  E1  E1.1, 1.2, 1.3  E1.4)hp(v/i)tigecpkyv(r/k)(s/t)(t/a)k (SEQ ID NO. 122) 1918, 25, 28, 30, 31,35, 47, 48, 51, 52, 55, 56, 57, 59, 63, 77, 79, 80, 81, 85, 87, 88, 89,91, 92, 95, 96, 97, 98, 99, 00 hdsnvknly(e/g)kv(k/r)(n/s)ql(k/r)nnak(SEQ ID NO. 123) 1918, 28, 30, 31, 77, 79, 80, 88, 91, 95, 98hdsnvknly(e/g)kv(k/r)(n/s)qlk (SEQ ID NO. 124) 1918, 28, 30, 31, 77, 79,80, 88, 91, 95, 98hkc(nn/dd)(a/t/e)cmesv(r/k)ngtydypkyseesklnre(e/k)idgvk (SEQ ID NO. 125)1918, 30, 35, 77, 80, 98 hkc(nn/dd)(a/t/e)cmesv(r/k)ngtydypkyseesk (SEQID NO. 126) 1918, 30, 35, 77, 80, 98hqn(e/g)qgsgyaadqkstqnai(d/n)gitnkvnsviekmntqftavgkefnklek (SEQ ID NO.127) 1918, 28, 30, 31, 35, 59, 79, 95hqn(e/g)qgsgyaadqkstqnai(d/n)gitnkvnsviek (SEQ ID NO. 128) 1918, 28, 30,31, 35, 59, 79, 95 hqn(e/g)qgsgyaadqkstqnai(d/n)gitnk (SEQ ID NO. 129)1918, 28, 30, 31, 35, 59, 79, 95 kfeifpktsswpnh (SEQ ID NO. 130) 1918,77 kg(n/s/t)sypkl(n/s)ksy(v/t)nnkgkevlvlwgvh (SEQ ID NO. 131) 1918, 35,77, 96 ksy(v/t)nnkgkevlvlwgvh (SEQ ID NO. 132) 1918, 35, 77, 96hkcnnecmesvkngtydypkyseesklnrekidgvk (SEQ ID NO. 133) 1928, 31, 95hkcnnecmesvkngtydypkyseesk (SEQ ID NO. 134) 1928, 31, 95hkcnnecmesvkngtydypk (SEQ ID NO. 135) 1928, 31, 95 hkcnnecmesvk (SEQ IDNO. 136) 1928, 31, 95 hngkssfy(k/r)nllwlt(e/g)knglypnlsksyvnnkek (SEQ IDNO. 137) 1928, 95, 00 hngkssfy(k/r)nllwlt(e/g)knglypnlsksyvnnk (SEQ IDNO. 138) 1928, 31, 95, 00 hngkssfy(k/r)nllwlt(e/g)knglypnlsk (SEQ ID NO.139) 1928, 31, 95, 00 hngkssfy(k/r)nllwlt(e/g)k (SEQ ID NO. 140) 1928,31, 95, 00 kssfyknllwlteknglypnlsksyvnnkekevlvlwgvh (SEQ ID NO. 141)1928, 31, 95 knllwlteknglypnlsksyvnnkekevlvlwgvh (SEQ ID NO. 142) 1928,31, 95 knglypnlsksyvnnkekevlvlwgvh (SEQ ID NO. 143) 1928, 31, 95, 96, 00ksy(v/a)nnkekev(l/-)(v/-)lwgvh (SEQ ID NO. 144) 1928, 31, 51, 95, 96,98, 00 kesswpnhtvtk (SEQ ID NO. 145) 1928, 31, 95het(t/n)kgvtaacpyagassfyrnllwlvkkensypklsksyvnnk (SEQ ID NO. 146) 1930,35 het(t/n)kgvtaacpyagassfyrnllwlvkkensypklsk (SEQ ID NO. 147) 1930, 35kfeifpktsswpnevlvlwgvh (SEQ ID NO. 148) 1930 kerswpkh (SEQ ID NO. 149)1947, 51, 52, 55, 56, 79, 82 klsksyvnnkekevlvlwqvh (SEQ ID NO. 150)1947, 51 knnkekevlvlwqvh (SEQ ID NO. 151) 1947h(k/n)(g/q)kssfy(r/k)nllwltekng(l/s)yp(n/t)lsksyannkek (SEQ ID NO. 152)1948 79, 89, 96 h(k/n)(g/q)kssfy(r/k)nllwltek (SEQ ID NO. 153) 1948 79,89, 96 hakkssfyk (SEQ ID NO. 154) 1951, 57, 59 hngklcrlkgk (SEQ ID NO.155) 1951, 52, 55, 56, 57, 59, 79, hyklnn(q/g)kk (SEQ ID NO. 156) 1956,00 hdiyrdeainnrfqiqgvkltqgyk (SEQ ID NO. 157) 1956 kgngcfeifhk (SEQ IDNO. 158) 1956 klnrliektndkyhqiek (SEQ ID NO. 159) 1956 klnrliektndkyh(SEQ ID NO. 160) 1956 kchtdkgslsttk (SEQ ID NO. 161) 1956kinngdyaklyiwgvh (SEQ ID NO. 162) 1956 hngklcrkgiaplqlgk (SEQ ID NO.163) 1959, 82 hetnrqvtaacpyagansffrnliwlvkkessypklsk (SEQ ID NO. 164)1963, 81 hetnrqvtaacpyagansffrnliwlvkkessypk (SEQ ID NO. 165) 1963, 81hpptstdqqslyqnadayifvgsskynrkfk (SEQ ID NO. 166) 1963, 81hpptstdqqslyqnadayifvgsskynrkfkpeia (SEQ ID NO. 167) 1963, 81hdiyrdeainnrfqiqgvkitqgyk (SEQ ID NO. 168) 1977, 79, 91hqneqgsgyaadqkstqnaidgitnkvnsviekmntqftavgk (SEQ ID NO. 169) 1977hqneqgsgyaadqkstqnaidgitnkvnsviek (SEQ ID NO. 170) 1977hqneqgsgyaadqkstqnaingitnkvnsviekmntqftavgkefnklek (SEQ ID NO. 171)1979, 91 hngklcrlkgiaplqlgk (SEQ ID NO. 172) 1979 hkcnnecmesvk (SEQ IDNO. 173) 1979 kfeifpkasswpnh (SEQ ID NO. 174) 1981 hdsnvknlyekvrsqlmnak(SEQ ID NO. 175) 1981 kvnsvikkmntqfaavgkefnh (SEQ ID NO. 176) 1981khngklck (SEQ ID NO. 177) 1981 kkgtsypklsksythnkgkevlvlwgvh (SEQ ID NO.178) 1981 kgtsypklsksythnkgkevlvlwgvh (SEQ ID NO. 179) 1981klsksythnkgkevlvlwgvh (SEQ ID NO. 180) 1981 ksythnkgkevlvlwgvh (SEQ IDNO. 181) 1981 kgvtascshk (SEQ ID NO. 182) 1985, 87kgvtascshkgrssfyrnllwlteknglypnlsk (SEQ ID NO. 183) 1985, 87kgnsypklsksyvnnkekevlvlwgih (SEQ ID NO. 184) 1988 kefnhlek (SEQ ID NO.185) 1988 hpptstdqqslyqnadayvfvgsskynkkfkpeiatrpk (SEQ ID NO. 186) 1988hpptstdqqslyqnadayvfvgsskynkkfk (SEQ ID NO. 187) 1988hegkssfyrnllwltekegsypklknsyvnk (SEQ ID NO. 188) 1991hegkssfyrnllwltekegsypk (SEQ ID NO. 189) 1991 hkcdnecmesvrngtydypkyseesk(SEQ ID NO. 190) 1991 kesswpnhtvtk (SEQ ID NO. 191) 1991, 92knllwlteknglypnlsksyvnnkekeilvlwgvh (SEQ ID NO. 192) 1991, 92, 96hngkssfy(k/m)(n/-)llwlt(e/g)(-/k)knglypnlsk (SEQ ID NO. 193) 1991, 92,96, 00 hngkssfyknllwltek (SEQ ID NO. 194) 1991, 92, 96htvtkgvtascshngkssfyknllwlteknglypnlsksyvnnkekevlvlwgvh (SEQ ID NO. 195)1995 htvt(k/g)gv(t/s)ascshngkssfy(k/m)(n/-)llwlt(e/g)k(-n/k)glypnlsk(SEQ ID NO. 196) 1995, 00 htvtkgvtascshngkssfyknllwltek (SEQ ID NO. 197)1995 kyvrstklrmvtglrnipsiqsrglfgaiagfieggwtgmidgwygyh (SEQ ID NO. 198)1995 hqneqgsgyaadqkstqnaingitnkvnsiiekmntqftavgk (SEQ ID NO. 199) 1995hqneqgsgyaadqkstqnaingitnkvnsiiek (SEQ ID NO. 200) 1995hqneqgsgyaadqkstqnaingitnk (SEQ ID NO. 201) 1995 hsgarsfyrnllwivkkgnsypk(SEQ ID NO. 202) 1996 hsgarsfyrnllwivkkgnsypklnk (SEQ ID NO. 203) 1996hsgarsfyrnllwivkkgnsypklnksytndk (SEQ ID NO. 204) 1996hsgarsfyrnllwivkkgnsypklnksytndkgk (SEQ ID NO. 205) 1996htvskgvttscshngk (SEQ ID NO. 206) 1996 katswpnhettk (SEQ ID NO. 207)1996 kqvttscshnqk (SEQ ID NO. 208) 1996 kgnsypklnksytndkgkevlviwgvh (SEQID NO. 209) 1996 klnksytndkgkevlviwgvh (SEQ ID NO. 210) 1996ksytndkgkevlviwgvh (SEQ ID NO. 211) 1996hnqkssfyrnllwlt(e/q)knglypnlsksy(v/a)annkek (SEQ ID NO. 212) 1997, 98,99 hpitigecpkyvrsak (SEQ ID NO. 213) 1997hqneqgsgyaadqkstqnaingitnkvnsviekmntqftavgk (SEQ ID NO. 214) 1998hqneqgsgyaadqkstqnaingitnkvnsviek (SEQ ID NO. 215) 1998hngkssfyrnllwlteknglypnlsksyvnnkek (SEQ ID NO. 216) 1998

[0291] TABLE 5 Replikin Sequences present in hemagglutinins of InfluenzaH2N2 viruses in years 1957-2000 Influenza H2N2 Replikins Year Detectedin Influenza H2N2 strain (Peak in FIG. 8: P2   E2) khfekvkilpk (SEQ IDNO. 217) 1957, 58, 59, 60, 61, 64, 65, 68, 78, 83, 84, 91 khllssvkhfekvk(SEQ ID NO. 218) 1957, 58, 59, 60, 61, 83, 84, 91ha(k/q/m)(d/n)ilekthngk (SEQ ID NO. 219) 1957, 58, 59, 60, 61, 64, 65,68, 78, 83, 84, 91, 95 ha(k/q/m)(d/n)ilekthngklc(k/r) (SEQ ID NO. 220)1957, 58, 59, 60, 61, 64, 65, 68, 78, 83, 84, 91, 95 hnvhpltigecpkyvksek(SEQ ID NO. 221) 1957, 58, 59, 65, 68 hpltigecpkyvksek (SEQ ID NO. 222)1957, 58, 59, 65, 68, 64, 65, 68, 78, 83, 84, 91 khllssvkhfekvkilpk (SEQID NO. 223) 1957, 58, 59, 60, 61, 64, 65, 68, 78krqssgimktegtlencetkcqtplgainttlpfhnvh (SEQ ID NO. 224) 1957, 59, 83kgsnyp(v/i)ak(g/r)synntsgeqmliiwq(v/i)h (SEQ ID NO. 225) 1957, 58, 59,61, 83, 91, 95 httlgqsracavsgnpsffrnmvwltekgsnypvak (SEQ ID NO. 226)1957 khfekvk (SEQ ID NO. 227) 1957, 59, 65kiskrgssgimktegtlencetkcqtplgainttlpfh (SEQ ID NO. 228) 1957, 59, 65, 91krgssgimktegtlencetkcqtplgainttlpfh (SEQ ID NO. 229) 1957, 59, 65, 91ktegtlencetkcqtplgainttlpfh (SEQ ID NO. 230) 1957, 59, 65, 91kiskrgssgimktegtlencetkcqtplgainttlpfh (SEQ ID NO. 231) 1957, 59, 65, 91ktegtlencetkcqtplgainttlpfhn(v/i)h (SEQ ID NO. 232) 1957, 59, 65, 91kiskrgssgimktegtlencetkcqtplgainttlpfh (SEQ ID NO. 233) 1957, 59, 65, 91k(e/g)snypvakgsynntsgeqmliiwgvh (SEQ ID NO. 234) 1957, 60, 65hpltigccpkyvksek (SEQ ID NO. 235) 1957, 60, 65 kcqtplgaikttlpfh (SEQ IDNO. 236) 1957, 65 hhsndqgsgyaadkestqka(f/i)dgitnkvnsviek- 1961, 65, 68,83, 84 mntqfeavgklf(n/s)nleklenlnkk (SEQ ID NO. 237)hsndqgsgyaadkestqka(f/i)dgitnkvnsviek- 1961 65, 68, 83, 84mntqfeavgklf(n/s)nleklenlnkk (SEQ ID NO. 238)hsndqgsgyaadkestqka(f/i)dgitnk (SEQ ID NO. 239) 1961, 65, 68, 83, 84hdsnvrnlydkvrmqlrdnak (SEQ ID NO. 240) 1964, 68, 76, 84, 91hkcddecmnsvkngtydypklnrneikgvk (SEQ ID NO. 241) 1964, 65, 68, 76, 83,84, 91 hkcddecmnsvkngtydypklnrneik (SEQ ID NO. 242) 1964, 65, 68, 76,83, 84, 91 hkcddecmnsvkngtydypk (SEQ ID NO. 243) 1964, 65, 68, 76, 83,84, 91 hkcddecmnsvk (SEQ ID NO. 244) 1964, 65, 68, 76, 83, 84, 91kgsnypvakgsynntngeqiliiwgvh (SEQ ID NO. 245) 1976, 78hsndqgsgyaadkestqkavdgitnkvnsviekmntqfeavgk (SEQ ID NO. 246) 1976, 91krgssgimktegtlencetkcqtplgainttlpfh (SEQ ID NO. 247) 1976, 78, 83, 84hpltigecpkyvksek (SEQ ID NO. 248) 1976 hakdilekthngklck (SEQ ID NO. 249)1976

[0292] TABLE 6 H3N2 Replikin Sequences present in H3N2 hemagglutinins ofInfluenza viruses in each year for which amino acid sequences wereavailable (1968-2000) Influenza H3N2 ReplikinsYear Detected in InfluenzaH3N2 strain Influenza Replikins (Peak in Figure 8: P3  E3  E4)hdvyrdealnnrfqikgvelksgyk (SEQ ID NO. 250) 1968, 72, 75 96, 97, 98htidltdsemnklfertrk (SEQ ID NO. 251) 1968 kfhqiek (SEQ ID NO. 252) 1968,72, 75, 77 96, 97, 98 ktnekfh(g/q)iek (SEQ ID NO. 253) 1968 86 98klnr(v/l)iektnekfh (SEQ ID NO. 254) 1968, 72, 75, 77 97, 98hqiekefsevegriqdlekyvedtk (SEQ ID NO. 255) 1968, 72, 98 kicnnphk (SEQ IDNO. 256) 1975 klnrvikktnekfh (SEQ ID NO. 257) 1975hd(l,v)yrdealnnrfqik(g/q)ve(r/k)s(q/g)yk (SEQ ID NO. 258) 1975, 76, 77,86 hqiekefsevegriqdlekyvedtk (SEQ ID NO. 259) 1975kyvedtkidlwsynaellvalenqh (SEQ ID NO. 260) 1975kyvkqnslklatgmrnvpekqtrglfgaiagfiengwegmidgwygfrh (SEQ ID NO. 261) 1975kefsevegriqdlekyvedtkidlwsynaellvalenqh (SEQ ID NO. 262) 1975 2000hqn(s/e)(e/q)g(t/s)g(q/y)aad(l/q)k- 1975 2000-stq(a/n)a(i/l)d(q/g)l(n/t)(g/n)k(l/v)n(r/s)vi(e/c)k (SEQ ID NO. 263)hcd(g/q)f(q,r)nekwdlf(v,/i)er(s/t)k (SEQ ID NO. 264) 1975, 76, 77, 78,80, 81, 82, 83, 84, 85, 86, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98htidltdsemnkklfertrk (SEQ ID NO. 265) 1977, ksgstypvlkvtmpnndnfdklyiwgvh(SEQ ID NO. 266) 1977 klnwltksgntypvlnvtmpnndnfdklviwgvh (SEQ ID NO.267) 1982 htidltdsemnklfektrk (SEQ ID NO. 268) 1986 klnrliektnekfhqtek(SEQ ID NO. 269) 1987 htgkssvmrsdapidfcnsecitpnqsipndkpfqnvnkitygacpk(SEQ ID NO. 270) 1994 htgkssvmrsdapidfcnsecitpnqsipndkpfqnvnk (SEQ IDNO. 271) 1994 hpstdsdqtslyvrasgrvtvstkrsqqtvipk (SEQ ID NO. 272) 1994kyvedtkidlwsynaellvalenqh (SEQ ID NO. 273) 1997, 98klfertrkqlrenaedmgngcfkiyh (SEQ ID NO. 274) 1998 krrsiksffsrlnwlh (SEQID NO. 275) 1998 hpvtigecpky(v/r)kstk (SEQ ID NO. 276) 2000kgnsypklsklsksyiinkkkevlviwgih (SEQ ID NO. 277) 2000klsklsks(v/y)iinkkkevlviwgih (SEQ ID NO. 278) 2000klsks(v/y)iinkkkevlviwgih (SEQ ID NO. 279) 2000

[0293] Both the concentration and type, i.e., composition of Replikinsobserved, were found to relate to the occurrence of influenza pandemicsand epidemics. The concentration of Replikins in influenza viruses wasexamined by visually scanning the hemagglutinin amino acid sequencespublished in the National Library of Medicine “PubMed” data base forinfluenza strains isolated world wide from human and animal reservoirsyear by year over the past century, i.e., 1900 to 2001. These Replikinconcentrations (number of Replikins per 100 amino acids, mean+/−SD) werethen plotted for each strain.

[0294] The concentration of Replikins was found to directly relate tothe occurrence of influenza pandemics and epidemics. The concentrationof Replikins found in influenza B hemagglutinin and influenza A strain,H1N1, is shown in FIG. 7, and the concentration of Replikins found inthe two other common influenza virus A strains, H2N2 and H3N2 is shownin FIG. 8 (H2N2, H3N2). The data in FIG. 8 also demonstrate an emergingnew strain of influenza virus as defined by its constituent Replikins(H3N2(R)).

[0295] Each influenza A strain has been responsible for one pandemic: in1918, 1957, and 1968, respectively. The data in FIGS. 7 and 8 show thatat least one Replikin per 100 amino acids is present in each of theinfluenza hemagglutinin proteins of all isolates of the four commoninfluenza viruses examined, suggesting a function for Replikins in themaintenance of survival levels of replication. In the 1990s, during thedecline of the H3N2 strain, there were no Replikins in many isolates ofH3N2, but a high concentration of new Replikins appeared in H3N2isolates, which define the emergence of the H3N2(R) strain.

[0296] Several properties of Replikin concentration are seen in FIG. 7and FIG. 8 to be common to all four influenza virus strains. First, theconcentration is cyclic over the years, with a single cycle of rise andfall occurring over a period of two to thirty years. This rise and fallis consistent with the known waxing and waning of individual influenzavirus strain predominance by hemagglutinin and neuramimidaseclassification. Second, peak Replikin concentrations of each influenzavirus strain previously shown to be responsible for a pandemic wereobserved to relate specifically and individually to each of the threeyears of the pandemics. For example, for the pandemic of 1918, where theinfluenza virus strain, H1N1, was shown to be responsible, a peakconcentration of the Replikins in H1N1 independently occurred (P1); forthe pandemic of 1957, where H2N2 emerged and was shown to beresponsible, a peak concentration of the Replikins in H2N2 occurred(P2); and for the pandemic of 1968, where H3N2 emerged and was shown tobe the cause of the pandemic, a peak concentration of the Replikins inH3N2 occurred (P3). Third, in the years immediately following each ofthe above three pandemics, the specific Replikin concentration decreasedmarkedly, perhaps reflecting the broadly distributed immunity generatedin each case. Thus, this post-pandemic decline is specific for H1N1immediately following the pandemic (P1) for which it was responsible,and is not a general property of all strains at the time. An increase ofReplikin concentration in influenza B repeatedly occurred simultaneouslywith the decrease in Replikin concentration in H1N1, e.g., EB1 in 1951and EB2 in 1976, both associated with influenza B epidemics having thehighest mortality. (Stuart-Harris, et al., Edward Arnold Ltd. (1985).Fourth, a secondary peak concentration, which exceeded the primary peakincrease in concentration, occurred 15 years after each of the threepandemics, and this secondary peak was accompanied by an epidemic: 15years after the 1918 pandemic in an H1N1 ‘epidemic’ year (E1); eightyears after the 1957 pandemic in an H2N2 ‘epidemic’ year (E2); andoccurred seven years after the 1968 pandemic in an H3N2 ‘epidemic’ year(E3). These secondary peak concentrations of specific Replikins mayreflect recovery of the strain. Fifth, peaks of each strain's specificReplikin concentration frequently appear to be associated with declinesin Replikin concentration of one or both other strains, suggestingcompetition between strains for host sites. Sixth, there is an apparentoverall tendency for the Replikin concentration of each strain todecline over a period of 35 years (H2N2) to 60 years (influenza B). Thisdecline cannot be ascribed to the influence of vaccines because it wasevident in the case of influenza B from 1901 to 1964, prior to commonuse of influenza vaccines. In the case of influenza B, Replikin recoveryfrom the decline is seen to occur after 1965, but Replikin concentrationdeclined again between 1997 and 2000 (FIG. 7). This correlates with thelow occurrence of influenza B in recent case isolates. H1N1 Replikinconcentration peaked in 1978-1979 (FIG. 7) together with thereappearance and prevalence of the H1N1 strain, and then peaked in 1996coincident with an H1N1 epidemic. (FIG. 7). H1N1 Replikin concentrationalso declined between 1997 and 2000, and the presence of H1N1 strainsdecreased in isolates obtained during these years. For H2N2 Replikins,recovery from a 35 year decline has not occurred (FIG. 8), and thiscorrelates with the absence of H2N2 from recent isolates. For H3N2, theReplikin concentration of many isolates fell to zero during the periodfrom 1996 to 2000, but other H3N2 isolates showed a significant, sharpincrease in Replikin concentration. This indicates the emergence of asubstrain of H3N2, which is designated herein as H3N2(R).

[0297]FIGS. 7 and 8 demonstrate that frequently, a one to three yearstepwise increase is observed before Replikin concentration reaches apeak. This stepwise increase proceeds the occurrence of an epidemic,which occurs concurrently with the Replikin peak. Thus, the stepwiseincrease in concentration of a particular strain is a signal thatparticular strain is the most likely candidate to cause an epidemic orpandemic.

[0298] Currently, Replikin concentration in the H3N2(R) strain ofinfluenza virus is increasing (FIG. 8, 1997 to 2000). Three similarprevious peak increases in H3N2 Replikin concentration are seen to haveoccurred in the H3N2-based pandemic of 1968 (FIG. 8), when the strainfirst emerged, and in the H3N2-based epidemics of 1972 and 1975 (FIG.8). Each of these pandemic and epidemics was associated with excessmortality. (Ailing, et al., Am J. Epidemiol.,113(1):30-43 (1981). Therapid ascent in concentration of the H3N2(R) subspecies of the H3N2Replikins in 1997-2000, therefore, statistically represents an earlywarning of an approaching severe epidemic or pandemic. An H3N2 epidemicoccurred in Russia in 2000 (FIG. 8, E4); and the CDC report of December2001 states that currently, H3N2 is the most frequently isolated strainof influenza virus world wide. (Morbidity and Mortality Weekly Reports(MMWR), Center for Disease Control; 50(48):1084-68 (Dec. 7, 2001).

[0299] In each case of influenza virus pandemic or epidemic newReplikins emerge. There has been no observation of two of the sameReplikins in a given hemagglutinin in a given isolate. To what degreethe emergence of a new Replikin represents mutations versus transferfrom another animal or avian pool is unknown. In some cases, each yearone or more of the original Replikin structures is conserved, while atthe same time, new Replikins emerge. For example, in influenza virus Bhemagglutinin, five Replikins were constantly conserved between 1919 and2001, whereas 26 Replikins came and went during the same period (somerecurred after several years absence). The disappearance andre-emergence years later of a particular Replikin structure suggeststhat the Replikins return from another virus host pool rather thanthrough de novo mutation.

[0300] In the case of H1N1 Replikins, the two Replikins present in theP1 peak associated with the 1918 pandemic were not present in therecovery E1 peak of 1933, which contains 12 new Replikins. Constantlyconserved Replikins, therefore, are the best choice for vaccines, eitheralone or in combination. However, even recently appearing Replikinsaccompanying one year's increase in concentration frequently persist andincrease further for an additional one or more years, culminating in aconcentration peak and an epidemic, thus providing both an early warningand time to vaccinate with synthetic Replikins (see for example, H1N1 inthe early 1990's, FIG. 7).

[0301] The data in FIGS. 7 and 8 demonstrate a direct relationshipbetween the presence and concentration of a particular Replikin ininfluenza protein sequences and the occurrence of pandemics andepidemics of influenza. Thus, analysis of the influenza virushemagglutinin protein sequence for the presence and concentration ofReplikins provides a predictor of influenza pandemics and/or epidemics,as well as a target for influenza vaccine formulation.

[0302] Composition of Replikins in Strains of Influenza Virus B: Of atotal of 26 Replikins identified in this strain (Table 3), the followingten Replikins are present in every influenza B isolate examined from1902-2001. Overlapping Replikin sequences are listed separately. Lysinesand histidines are in bold type to demonstrate homology consistent withthe “3-point recognition.”

[0303] kshfanlk (SEQ ID NO. 91)

[0304] kshfanlkgtk (SEQ ID NO. 92)

[0305] kshfanlkgtktrgklcpk (SEQ ID NO. 93)

[0306] hekygglnk (SEQ ID NO. 94)

[0307] hekygglnksk (SEQ ID NO. 95)

[0308] hekygglnkskpyytgehak (SEQ ID NO. 96)

[0309] hakaigncpiwvk (SEQ ID NO. 97)

[0310] hakaigncpiwvvkktplklangtk (SEQ ID NO. 98)

[0311] hakaigncpiwvktplklangtkyrppak (SEQ ID NO. 99)

[0312] hakaigncpiwvktplklangtkyrppakllk (SEQ ID NO. 100)

[0313] Tables 3 and 4 indicate that there appears to be much greaterstability of the Replikin structures in influenza B hemagglutininscompared with H1N1 Replikins. Influenza B has not been responsible forany pandemic, and it appears not to have an animal or avian reservoirs.(Stuart-Harris et al., Edward Arnold Ltd., London (1985)).

[0314] Influenza H1N1 Replikins: Only one Replikin“hp(v/i)tigecpkyv(r/k)(s/t)(t/a)k” is present in every H1N1 isolate forwhich sequences are available from 1918, when the strain first appearedand caused the pandemic of that year, through 2000 (Table 4) (“(v/i)”indicates that the amino acid v or i is present in the same position indifferent years.) Although H1N1 contains only one persistent Replikin,H1N1 appears to be more prolific than influenza B. There are 95different Replikin structures in 82 years on H1N1 versus only 31different Replikins in 100 years of influenza B isolates (Table 4). Anincrease in the number of new Replikin structures occurs in years ofepidemics (Tables 3, 4, 5 and 6) and correlates with increased totalReplikin concentration (FIGS. 7 and 8).

[0315] Influenza H2N2 Replikins: Influenza H2N2 was responsible for thehuman pandemic of 1957. Three of the 20 Replikins identified in thatstrain for 1957 were conserved in each of the H2N2 isolates availablefor examination on PubMed until 1995 (Table 5).

[0316] ha(k/q/m)(d/n)ilekthngk (SEQ ID NO. 219)

[0317] ha(k/q/m)(d/n)ilekthngklc(k/r) (SEQ ID NO. 220)

[0318] kgsnyp(v/i)ak(g/r)synntsgeqmliiwq(v/i)h (SEQ ID No. 225)

[0319] However, in contrast to H1N1, only 13 additional Replikins havebeen found in H2N2 beginning in 1961. This paucity of appearance of newReplikins correlates with the decline in the concentration of the H2N2Replikins and the appearance of H2N2 in isolates over the years (FIG.8).

[0320] Influenza H3N2 Replikins: Influenza H3N2 was responsible for thehuman pandemic of 1968. Five Replikins which appeared in 1968disappeared after 1977, but reappeared in the 1990s (Table 6). The onlyReplikin structure which persisted for 22 years washcd(g/q)f(q/r)nekwdlf(v/i)er(s/t)_(k), which appeared first in 1977 andpersisted through 1998. The emergence of twelve new H3N2 Replikins inthe mid 1990s (Table 6) correlates with the increase in Replikinconcentration at the same time (FIG. 8), and with the prevalence of theH3N2 strain in recent isolates together with the concurrentdisappearance of all Replikins from some of these isolates (FIG. 8),this suggests the emergence of the new substrain H3N2(R).

[0321]FIGS. 1 and 2 show that influenza epidemics and pandemicscorrelate with the increased concentration of Replikins in influenzavirus, which is due to the reappearance of at least one Replikin fromone to 59 years after its disappearance. Also, in the A strain only,there is an emergence of new strain-specific Replikin compositions(Tables 4-6). Increase in Replikin concentration by repetition ofindividual Replikins within a single protein appears not to occur ininfluenza virus, but is seen in other organisms.

[0322] It has been believed that changes in the activity of differentinfluenza strains are related to sequence changes in influenzahemagglutinins, which in turn are the products of substitutions effectedby one of two poorly understood processes: i) antigenic drift, thoughtto be due to the accumulation of a series of point mutations in thehemagglutinin molecule, or ii) antigenic shift, in which the changes areso great that genetic reassortment is postulated to occur between theviruses of human and non-human hosts. First, the present data suggeststhat the change in activity of different influenza strains, rather thanbeing related to non-specific sequence changes, are based upon, orrelate to the increased concentration of strain-specific Replikins andstrain-specific increases in the replication associated with epidemics.In addition, the data were examined for a possible insight into whichsequence changes are due to “drift” or “shift”, and which are due toconservation, storage in reservoirs, and reappearance. The data showthat the epidemic-related increase in Replikin concentration is not dueto the duplication of existing Replikins per hemagglutinin, but is dueto the reappearance of at least one Replikin composition from 1 to up to59 years after its disappearance, plus in the A strains only, theemergence of new strain-specific Replikin compositions (Tables 3-6).Thus the increase in Replikin concentration in the influenza B epidemicsof 1951 and 1977 are not associated with the emergence of new Replikincompositions in the year of the epidemic but only with the reappearanceof Replikin compositions which had appeared in previous years thendisappeared (Table 3). In contrast, for the A strains, in addition tothe reappearance of previously disappeared virus Replikins, newcompositions appear (e.g. in H1N1 in the year of the epidemic of 1996,in addition to the reappearance of 6 earlier Replikins, 10 newcompositions emerged). Since the A strains only, not influenza B, haveaccess to non-human animal and avian reservoirs, totally newcompositions probably derive from non-human host reservoirs rather thanfrom mutations of existing human Replikins which appear to bear noresemblance to the new compositions other than the basic requirements of“3-point recognition” (Tables 2-5). The more prolific nature of H1N1compared with B, and the fact that pandemics have been produced by thethree A strains only, but not by the B strain, both may also be afunction of the ability of the human A strains to receive new Replikincompositions from non-human viral reservoirs.

[0323] Some Replikins have appeared in only one year, disappeared, andnot reappeared to date (Tables 3-6). Other Replikins disappear from oneto up to 81 years, when the identical Replikin sequence reappears. KeyReplikin ‘k’ and ‘h’ amino acids, and the spaces between them, areconserved during the constant presence of particular Replikins over manyyears, as shown in Tables 23-6 for the following strain-specificReplikins: ten of influenza B, the single Replikin of H1N1, and thesingle Replikin of H2N3, as well as for the reappearance of identicalReplikins after an absence. Despite the marked replacement orsubstitution activity of other amino acids both inside the Replikinstructure and outside it in the rest of the hemagglutinin sequences,influenza Replikin histidine (h) appears never to be, and lysine (k) israrely replaced. Examples of this conservation are seen in the H1N1Replikin “hp(v/i)tigecpkyv(r/k)(s/t)(t/a)k,” (SEQ ID NO. 122) constantbetween 1918 and 2000, in the H3N2 Replikin“hcd(g/q)f(q,r)nekwdlf(v/i)er(s/t)k” (SEQ ID NO. 264) constant between1975 and 1998 and in the H3N2 Replikin“hqn(s/e)(e/q)g(t/s)g(q/y)aad(l/q)kstq(a/n)a(i/l)d(q/g)I(n/t)(g/n)k(l/v)n(r/s)vi(e/c)k” (SEQ ID NO. 263) which first appeared in 1975, disappeared for25 years, and then reappeared in 2000. While many amino acids weresubstituted, the basic Replikin structure of 2 Lysines, 6 to 10 residuesapart, one histidine, a minimum of 6% lysine in not more thanapproximately 50 amino acids, was conserved.

[0324] Totally random substitution would not permit the persistence ofthese H1N1 and H3N2 Replikins, nor from 1902 to 2001 in influenza B thepersistence of 10 Replikin structures, nor the reappearance in 1993 of a1919 18 mer Replikin after an absence of 74 years. Rather than a randomtype of substitution, the constancy suggests an orderly controlledprocess, or in the least, protection of the key Replikin residues sothat they are fixed or bound in some way: lysines, perhaps bound tonucleic acids, and histidines, perhaps bound to respiratory redoxenzymes. The mechanisms which control this conservation are at presentunknown.

Conservation of Replikin Structures

[0325] Whether Replikin structures are conserved or are subject toextensive natural mutation was examined by scanning the proteinsequences of various isolates of foot and mouth disease virus (FMDV),where mutations in proteins of these viruses have been well documentedworldwide for decades. Protein sequences of FMDV isolates were visuallyexamined for the presence of both the entire Replikin and each of thecomponent Replikin amino acid residues observed in a particularReplikin.

[0326] Rather than being subject to extensive substitution over time asoccurs in neighboring amino acids, the amino acids which comprise theReplikin structure are substituted little or not at all, that is theReplikin structure is conserved.

[0327] For example, in the protein VP1 of FMDV type O, the Replikin (SEQID NO.: 3) “hkqkivapvk” was found to be conserved in 78% of the 236isolates reported in PubMed, and each amino acid was found to beconserved in individual isolates as follows: his, 95.6%; lys, 91.8%; gin92.3%; lys, 84.1%; ile, 90.7%; val, 91.8%; ala, 97.3%; pro, 96.2%; ala,75.4%; and lys, 88.4%. The high rate of conservation suggests structuraland functional stability of the Replikin structure and provides constanttargets for treatment.

[0328] Similarly, sequence conservation was found in different isolatesof HIV for its Replikins, such as (SEQ ID NO.: 5) “kcfncgkegh” or (SEQID NO.: 6) “kvylawvpahk” in HIV Type 1 and (SEQ ID NO.: 7) “kcwncgkegh”in HIV Type 2 (Table 2). Further examples of sequence conservation werefound in the HIV tat proteins, such as (SEQ ID NO.: 698)“hclvckqkkglgisygrkk,” wherein the key lysine and histaidine amino acidsare conserved (See Table 7).

[0329] Similarly, sequence conservation was observed in plants, forexample in wheat, such as in wheat ubiguitin activating enzyme E (SEQ IDNOs. 601-603). The Replikins in wheat even provided a reliable targetfor stimulation of plant growth as described within. Other examples ofconservation are seen in the constant presence of malignin in successivegenerations, over ten years of tissue culture of glioma cells, and bythe constancy of affinity of the glioma Replikin for antimaligninantibody isolated by immunoadsorption from 8,090 human sera from theU.S., U.K., Europe and Asia (e.g., FIG. 5 and U.S. Pat. No. 6,242,578B1).

[0330] Similarly, conservation was observed in trans-activator (Tat)proteins in isolates of HIV. Tat (trans-activator) proteins are earlyRNA binding proteins regulating lentiviral transcription. These proteinsare necessary components in the life cycle of all known lentivirases,such as the human immunodeficiency viruses (HIV). Tat is atranscriptional regulator protein that acts by binding to thetransactivating response sequence (TAR) RNA element and activatestranscription Initiation and/or elongation from the LTR promoter. HIVcannot replicate without tat, but the chemical basis of this has beenunknown. In the HIV tat protein sequence from 89 to 102 residues, wehave found a Replikin that is associated with rapid replication in otherorganisms. The amino acid sequence of this Replikin is“hclvcfqkkglgisygrkk.” In fact, we found that this Replikin is presentin every HIV tat protein. Some tat amino acids are substitutedfrequently, as shown in Table 8, by alternate amino acids (in small sizefonts lined up below the most frequent amino acid (Table 7), thepercentage of conservation for the predominant Replikin“hclvcfqkkglgisygrkk”). These substitutions have appeared for most ofthe individual amino acids. However, the key lysine and histidine aminoacids within the Replikin sequence, which define the Replikin structure,are conserved 100% in the sequence; while substitutions are commonelsewhere in other amino acids, both within and outside the Replikin,none occurs on these key histidine amino acids.

[0331] As shown in Table 7, it is not the case that lysines are notsubstituted in the tat protein amino acid sequence. From the left sideof the table, the very first lysine in the immediate neighboringsequence, but outside the Replikin sequence, and the second lysine (k)in the sequence inside the Replikin, but “extra” in that it is notessential for the Replikin formation, are both substituted frequently.However, the 3rd, 4th and 5th lysines, and the one histidine, inparentheses, which together set up the Replikin structure, are neversubstituted. Thus, these key amino acid sequences are 100% conserved. Asobserved in the case of the influenza virus Replikins, randomsubstitution would not permit this selective substitution and selectivenon-substitution to occur due to chance. TABLE 7 % Replikin CONSERVATIONof each constituent amino acid in the first 117 different isolates ofHIV tat protein as reported in PubMed: 38 100 57 86 100 100 66 76 100 9957 49 100 94 100 97 98 85 97 99 100 100 100% Neighboring- Amino acids[tat Replikin] k (c) s y [(h) (c) l v (c) f q k (k) g (l) g i s y g (r)(k) (k)] below are the amino acid substitutions observed for each aminoacid above: h c f q i l h t a a l y h q r w p l l i h q v y s s l m r si s m s s r n v a f p q

[0332] The conservation of the Replikin structure suggests that theReplikin structure has a specific survival function for the HIV viruswhich must be preserved and conserved, and cannot be sacrificed to thevirus ‘defense’ maneuver of amino acid substitution crested to avoidantibody and other ‘attack.’ These ‘defense’ functions, although alsoessential, cannot ‘compete’ with the virus survival function of HIVreplication.

[0333] Further conservation was observed in different isolates of HIVfor its Replikins such as “kcfncgkegh” (SEQ ID NO. 5) or “kvylawvpahk”(SEQ ID NO. 6) in HIV Type 1 and “kcwncgkegh” (SEQ ID NO. 7) in HIV Type2.

[0334] The high rate of conservation observed in FMVD and HIV Replikinssuggests that conservation also observed in the Replikins of influenzaReplikins is a general property of viral Replikins. This conservationmakes them a constant and reliable tarted for either destruction, forexample by using specific Replikins such as for influenza, FMVD or HIVvaccines as illustrated for the glioma Replikin, or stimulation.

[0335] Similarly, as provided in examples found in viruses includinginfluenza viruses, FMDV, and HIV, where high rates of conservation inReplikins suggest that conservation is a general property of viralReplikins and thus making Replikins a constant and reliable target fordestruction or stimulation, conservation of Replikin structures occursin plants. For example, in wheat plants, Replikins are conserved andprovide a reliable target for stimulation. Examples of conservedReplikins in wheat plants ubiquitin activating enzyme E include:

[0336] E3 hkdrltkkvvdiarevakvdvpeyrrh (SEQ ID NO. 601)

[0337] E2 hkerldrkvvdvarevakvevpsyrrh (SEQ ID NO. 602)

[0338] E1 hkerldrkvvdvarevakmevpsyrrh (SEQ ID NO. 603)

[0339] Similarly to conservation found in the HIV tat protein, theReplikin in the wheat ubiquitin activating enzyme E is conserved. Aswith the HIV tat protein, substitutions of amino acids (designated withan ‘*’) adjacent to the Replikin variant forms in wheat ubiquitinactivating enzyme E are common. The key k and h amino acids that formthe Replikin structure, however, do not vary whereas the ‘unessential’ kthat is only 5 amino acids (from the first k on the left) issubstituted.

Anti-Replikin Antibodies

[0340] An anti-Replikin antibody is an antibody against a Replikin. Dataon anti-Replikin antibodies also support Replikin class unity. Ananti-Replikin antibody response has been quantified by immunoadsorptionof serum antimalignin antibody to immobilized malignin (see Methods inU.S. Pat. No. 5,866,690). The abundant production of antimaligninantibody by administration to rabbits of the synthetic version of the16-mer peptide whose sequence was derived from malignin, absentcarbohydrate or other groups, has established rigorously that thispeptide alone is an epitope, that is, provides a sufficient basis forthis immune response (FIG. 3). The 16-mer peptide produced both IgM andIgG forms of the antibody. Antimalignin antibody was found to beincreased in concentration in serum in 37% of 79 cases in the U.S. andAsia of hepatitis B and C, early, in the first five years of infection,long before the usual observance of liver cancer, which develops aboutfifteen to twenty-five years after infection. Relevant to bothinfectious hepatitis and HIV infections, transformed cells may be oneform of safe haven for the virus: prolonging cell life and avoidingvirus eviction, so that the virus remains inaccessible to anti-viraltreatment.

[0341] Because administration of Replikins stimulates the immune systemto produce antibodies having a cytotoxic effect, peptide vaccines basedon the particular influenza virus Replikin or group of Replikinsobserved to be most concentrated over a given time period provideprotection against the particular strain of influenza most likely tocause an outbreak in a given influenza season., e.g., an emerging strainor re-emerging strain For example, analysis of the influenza virushemagglutinin amino acid sequence on a yearly or bi-yearly basis,provides data which are useful in formulating a specifically targetedinfluenza vaccine for that year. It is understood that such analysis maybe conducted on a region-by-region basis or at any desired time period,so that strains emerging in different areas throughout the world can bedetected and specifically targeted vaccines for each region can beformulated.

[0342] Influenza

[0343] Currently, vaccine formulations are changed twice yearly atinternational WHO and CDC meetings. Vaccine formulations are based onserological evidence of the most current preponderance of influenzavirus strain in a given region of the world. However, prior to thepresent invention there has been no correlation of influenza virusstrain specific amino acid sequence changes with occurrence of influenzaepidemics or pandemics.

[0344] The observations of specific Replikins and their concentration ininfluenza virus proteins provides the first specific quantitative earlychemical correlates of influenza pandemics and epidemics and providesfor production and timely administration of influenza vaccines tailoredspecifically to treat the prevalent emerging or re-emerging strain ofinfluenza virus in a particular region of the world. By analyzing theprotein sequences of isolates of strains of influenza virus, such as thehemagglutinin protein sequence, for the presence, concentration and/orconservation of Replikins, influenza virus pandemics and epidemics canbe predicted. Furthermore, the severity of such outbreaks of influenzacan be significantly lessened by administering an influenza peptidevaccine based on the Replikin sequences found to be most abundant orshown to be on the rise in virus isolates over a given time period, suchas about one to about three years.

[0345] An influenza peptide vaccine of the invention may include asingle Replikinpeptide sequence or may include a plurality of Replikinsequences observed in influenza virus strains. Preferably, the peptidevaccine is based on Replikin sequence(s) shown to be increasing inconcentration over a given time period and conserved for at least thatperiod of time. However, a vaccine may include a conserved Replikinpeptide(s) in combination with a new Replikin(s) peptide or may be basedon new Replikin peptide sequences. The Replikin peptides can besynthesized by any method, including chemical synthesis or recombinantgene technology, and may include non-Replikin sequences, althoughvaccines based on peptides containing only Replikin sequences arepreferred. Preferably, vaccine compositions of the invention alsocontain a pharmaceutically acceptable carrier and/or adjuvant.

[0346] The influenza vaccines of the present invention can beadministered alone or in combination with antiviral drugs, such asgancyclovir; interferon; interleukin; M2 inhibitors, such as,amantadine, rimantadine; neuramimidase inhibitors, such as zanamivir andoseltamivir; and the like, as well as with combinations of antiviraldrugs.

Replikin Decoys in Malaria

[0347] Analysis of the primary structure of a Plasmodium falciparummalaria antigen located at the merozoite surface and/or within theparasitophorous vacuole revealed that this organism, like influenzavirus, also contains numerous Replikins (Table 8). However, there areseveral differences between the observation of Replikins in Plasmodiumfalciparum and influenza virus isolates. For example, Plasmodiumfalciparum contains several partial Replikins, referred to herein as“Replikin decoys.” These decoy structures contain an abundance of lysineresidues, but lack the histidine required of Replikin structures.Specifically, these decoys contain many lysines 6 to 10 residues apartin overlapping fashion, similar to the true malaria recognins butwithout histidine residues. It is believed that the decoy structuremaximizes the chances that an anti-malarial antibody or other agent willbind to the relatively less important structure containing the lysines,i.e., the Replikin decoys, rather than binding to histidine, which ispresent in Replikin structure, such as Replikins in respiratory enzymes,which could result in destruction of the trypanosome. For example, anincoming antibody, with specificity for Replikin structures, mightattach to the Replikin decoy structure, leaving the true Replikinstructure remains untouched.

[0348] Therefore, anti-Replikin treatment of malaria requires two phases(dual treatment): i) preliminary treatment with proteolytic enzymes thatcleave the Replikin decoys, permitting ‘safe passage’ of the specificanti-Replikin treatment; and ii) attacking malaria Replikins either withspecific antibodies or by cellular immunity engendered by syntheticmalaria Replikin vaccines or by organic means targeting the malariaReplikins.

Repetition and Overlapping of Replikin Structures

[0349] Another difference seen in Plasmodium falciparum is a frequentrepetition of individual Replikin structures within a single protein,which was not observed with influenza virus. Repetition may occur by (a)sharing of lysine residues between Replikins, and (b) by repetition of aportion of a Replikin sequence within another Replikin sequence.

[0350] A third significant difference between Replikin structuresobserved in influenza virus isolates and Plasmodium falciparum is amarked overlapping of Replikin structures throughout malarial proteins,e.g., there are nine overlapping Replikins in the 39 amino acid sequenceof SEQ ID NO. 380 (Replikin concentration=23.1/100 amino acids); and 15overlapping Replikins in the 41 amino acids of SEQ ID NO. 454 (Replikinconcentration=36.6/100 amino acids). Both of these overlapping Replikinstructures occur in blood stage trophozoites and schizonts. In contrast,influenza virus Replikins are more scattered throughout the protein andthe maximum Replikin concentration is about 7.5/100 amino acids (FIG.7); and tomato leaf curl gemini virus, which was also observed to haveoverlapping Replikins has only about 3.1/100 amino acids.

[0351] This mechanism of lysine multiples is also seen in the Replikinsof cancer proteins such as in gastric cancer transforming protein,ktkkgnrvsptmkvth (SEQ ID NO. 88), and in transforming protein P21B(K-RAS 2B) of lung, khkekmskdgkkkkkks (SEQ ID NO. 89).

[0352] The relationship of higher Replikin concentration to rapidreplication is also confirmed by analysis of HIV isolates. It was foundthat the slow-growing low titer strain of HIV (NSI, “Bru,” which isprevalent in early stage HIV infection) has a Replikin concentration of1.1 (+/−1.6) Replikins per 100 amino acids, whereas the rapidly-growinghigh titer strain of HIV (SI, “Lai”, which is prevalent in late stageHIV infection) has a Replikin concentration of 6.8 (+/−2.7) Replikinsper 100 amino acid residues.

[0353] The high concentration of overlapping Replikins in malaria,influenza virus and cancer cells is consistent with the legendary highand rapid replicating ability of malaria organisms. The multitude ofoverlapping Replikins in malaria also provides an opportunity for theorganism to flood and confuse the immune system of its host and therebymaximize the chance that the wrong antibody will be made andperpetuated, leaving key malaria antigens unharmed.

[0354] As in the case of influenza virus, for example, peptide vaccinesbased on the Replikin structure(s) found in the malaria organism canprovide an effective means of preventing and/or treating malaria.Vaccination against malaria can be achieved by administering acomposition containing one or a mixture of Replikin structures observedin Plasmodium falciparum. Furthermore, antibodies to malaria Replikinscan be generated and administered for passive immunity or malariadetection

[0355] Table 8 provides a list of several Plasmodium falciparum Replikinsequences. It should be noted that this list is not meant to becomplete. Different isolates of the organism may contain other Replikinstructures. TABLE 8 Malaria Replikins a) Primary structure of aPlasmodium falciparum malaria antigen located at the merozoite surfaceand within the parasitophorous vacuole a) i) DECOYS: (C-Terminal)keeeekekekekekeekekeekekeekekekeekekekeekeeekk (SEQ ID NO. 280), orkeeeekekekekekeekekeekekeekekekeekekekeekeeekkek (SEQ ID NO. 281), orkeeeekekekekekeekekeekekekeekekeekekeekeekeeekk (SEQ ID NO. 282), orkeeeekekek (SEQ ID NO. 283) ii) ReplikinS: Hkklikalkkniesiqnkk (SEQ IDNO. 284) hkklikalkkniesiqnkm (SEQ ID NO. 285) hkklikalkk (SEQ ID NO.286) hkklikalk (SEQ ID NO. 287) katysfvntkkkiislksqghkk (SEQ ID NO. 288)katysfvntkkkiislksqghk (SEQ ID NO. 289) katysfvntkkkiislksqgh (SEQ IDNO. 290) htyvkgkkapsdpqca dikeeckellkek (SEQ ID NO. 291) kiislksqghk(SEQ ID NO. 292) kkkkfeplkngnvsetiklih (SEQ ID NO. 293)kkkfeplkngnvsetiklih (SEQ ID NO. 294) kkfeplkngnvsetiklih (SEQ ID NO.295) kngnvsetiklih (SEQ ID NO. 296) klihlgnkdkk (SEQ ID NO. 297)kvkkigvtlkkfeplkngnvsetiklihlgnkdkkh (SEQ ID NO. 298)hliyknksynplllscvkkmnmlkenvdyiqnqnlfkelmnqkatysfvntkkkiislk (SEQ ID NO.299) hliyknksynplllscvkkmnmlkenvdyiqnqnlfkelmnqkatysfvntk (SEQ ID NO.300) hliyknksynplllscvkkmnmlkenvdyiqnqnlfkelmnqk (SEQ ID NO. 301)hliyknksynplllscvkkmnmlkenvdyiqknqnlfk (SEQ ID NO. 302)hliyknksynplllscvkkmnmlk (SEQ ID NO. 303)ksannsanngkknnaeemknlvnflqshkklikalkkniesiqnkkh (SEQ ID NO. 304)kknnaeemknlvnflqshkklikalkkniesiqnkkh (SEQ ID NO. 305)knlvnflqshkklikalkkniesiqnkkh (SEQ ID NO. 306) kklikalkkniesiqnkkh (SEQID NO. 307) klikalkkniesiqnkkh (SEQ ID NO. 308) kkniesiqnkkh (SEQ ID NO.309) kniesiqnkkh (SEQ ID NO. 310) knnaeemknlvnflqsh (SEQ ID NO. 311)kklikalkkniesiqnkkqghkk (SEQ ID NO. 312) kknnaeemknlvnflqshk (SEQ ID NO.313) knnaeemknlvnflqsh (SEQ ID NO. 314) klikalkkniesiqnkkqghkk (SEQ IDNO. 315) kvkkigvtlkkfeplkngnvsetiklih (SEQ ID NO. 316) kngnvsetiklih(SEQ ID NO. 317) klihlgnkdkk (SEQ ID NO. 318)ksannsanngkknnaeemknlvnflqsh (SEQ ID NO. 319) kknnaeemknlvnflqsh (SEQ IDNO. 320) kklikalkkniesiqnkkh (SEQ ID NO. 321) kalkkniesiqnkkh (SEQ IDNO. 322) kkniesiqnkkh (SEQ ID NO. 323) kelmnqkatysfvntkkkiislksqgh (SEQID NO. 324) ksqghkk (SEQ ID NO. 325) kkkiislksqgh (SEQ ID NO. 326)kkiislksqgh (SEQ ID NO. 327) kkniesiqnkkh (SEQ ID NO. 328) kniesiqnkkh(SEQ ID NO. 329) htyvkgkkapsdpqcadikeeckellkek (SEQ ID NO. 330)htyvkgkkapsdpqcadikeeckellk (SEQ ID NO. 331) b)“liver stage antigen-3”gene = “LSA-3” Replikins henvlsaalentqseeekkevidvieevk (SEQ ID NO. 332)kenvvttilekveettaesvttfsnileeiqentitndtieekleelh (SEQ ID NO. 333)hylqqmkekfskek (SEQ ID NO. 334)hylqqmkekfskeknnnvievtnkaekkgnvqvtnktekttk (SEQ ID NO. 335)hylqqmkekfskeknnnvievtnkaekkgnvqvtnktekttkvdknnk (SEQ ID NO. 336)hylqqmkekfskeknnnvievtnkaekkgnvqvtnktekttkvdknnkvpkkrrtqk (SEQ ID NO.337) hylqqmkekfskeknnnvievtnkaekkgnvqvtnktekttkvdknnkvpkkrrtqksk (SEQ IDNO. 338) hvdevmkyvqkidkevdkevskaleskndvtnvlkqnqdffskvknfvkkyk (SEQ IDNO. 339) hvdevmkyvqkidkevdkevskaleskndvtnvlkqnqdffskvknfvkk (SEQ ID NO.340) hvdevmkyvqkidkevdkevskaleskndvtnvlkqnqdffsk (SEQ ID NO. 341)hvdevmkyvqkidkevdkevskaleskndvtnvlk (SEQ ID NO. 342)hvdevmkyvqkidkevdkevskalesk (SEQ ID NO. 343) hvdevmkyvqkidkevdkevsk (SEQID NO. 344) hvdevmkyvqkidkevdk (SEQ ID NO. 345) hvdevmkyvqkidk (SEQ IDNO. 346) kdevidlivqkekriekvkakkkklekkveegvsglkkh (SEQ ID NO. 347)kvkakkkklekkveegvsglkkh (SEQ ID NO. 348) kakkkklekkveegvsglkkh (SEQ IDNO. 349) kkkklekkveegvsglkkh (SEQ ID NO. 350) kkklekkveegvsglkkh (SEQ IDNO. 351) kklekkveegvsglkkh (SEQ ID NO. 352) klekkveegvsglkkh (SEQ ID NO.353) kkveegvsglkkh (SEQ ID NO. 354) kveegvsglkkh (SEQ ID NO.355)hveqnvyvdvdvpamkdqflgilneagglkemffnledvfksesdvitveeikdepvqk (SEQ ID NO.356) hikgleeddleevddlkgsildmlkgdmelgdmdkesledvttklgerveslk (SEQ ID NO.357) hikgleeddleevddlkgsildmlkgdmelgdmdkesledvttk (SEQ ID NO. 358)hikgleeddleevddlkgsildmlkgdmelgdmdk (SEQ ID NO. 359)hikgleeddleevddlkgsildmlk (SEQ ID NO. 360)hiisgdadvlssalgmdeeqmktrkkaqrpk (SEQ ID NO. 361) hditttldevvelkdveedkiek(SEQ ID NO. 362) kkleevhelk (SEQ ID NO. 363) kleevhelk (SEQ ID NO. 364)ktietdileekkkeiekdh (SEQ ID NO. 365) kkeiekdhfek (SEQ ID NO. 366) kdhfek(SEQ ID NO. 367) kfeeeaeeikh (SEQ ID NO. 368) c) 28 KDA ookinete surfaceantigen precursor Replikins:kdgdtkctlecaqgkkcikhksdhnhksdhnhksdpnhkkknnnnnk (SEQ ID NO. 369)kdgdtkctlecaqgkkcikhksdhnhksdhnhksdpnhkk (SEQ ID NO. 370)kdgdtkctlecaqgkkcikhksdhnhksdhnhksdpnhk (SEQ ID NO. 371)kdgdtkctlecaqgkkcikhksdhnhksdhnhk (SEQ ID NO. 372)kdgdtkctlecaqgkkcikhksdhnhk (SEQ ID NO. 373) kdgdtkctlecaqgkkcikhk (SEQID NO. 374) kdgdtkctlecaqgkk (SEQ ID NO. 375) kdgdtkctlecaqgk (SEQ IDNO. 376) kciqaecnykecgeqkcvwdgih (SEQ ID NO. 377) kecgeqkcvwdgih (SEQ IDNO. 378) hieckcnndyvltnryecepknkctsledtnk (SEQ ID NO. 379) d) Bloodstage trophozoites and schizonts Replikins:ksdhnhksdhnhksdhnhksdhnhksdpnhkkknnnnnk (SEQ ID NO. 380)ksdhnhksdhnhksdhnhksdpnhkkknnnnnk (SEQ ID NO. 381)ksdhnhksdhnhksdpnhkkknnnnnk (SEQ ID NO. 382) ksdhnhksdpnhkkknnnnnk (SEQID NO. 383) kkknnnnnkdnksdpnhk (SEQ ID NO. 384) kknnnnnkdnksdpnhk (SEQID NO. 385) knnnnnkdnksdpnhk (SEQ ID NO. 386) kdnksdpnhk (SEQ ID NO.387) ksdpnhk (SEQ ID NO. 388) hslyalqqneeyqkvknekdqneikkikqlieknk (SEQID NO. 389) hslyalqqneeyqkvknekdqneikkik (SEQ ID NO. 390)hslyalqqneeyqkvknekdqneikk (SEQ ID NO. 391) hslyalqqneeyqkvknekdqneik(SEQ ID NO. 392) hklenleemdk (SEQ ID NO. 393) khfddntneqk (SEQ ID NO.394) kkeddekh (SEQ ID NO. 395) keennkkeddekh (SEQ ID NO. 396)ktssgilnkeennkkeddekh (SEQ ID NO. 397) knihikk (SEQ ID NO. 398)hikkkegidigyk (SEQ ID NO. 399) kkmwtcklwdnkgneitknih (SEQ ID NO. 400)kkgiqwnllkkmwtcklwdnkgneitknih (SEQ ID NO. 401)kekkdsnenrkkkqkedkknpnklkkieytnkithffkaknnkqqnnvth (SEQ ID NO. 402)kkdsnenrkkkqkedkknpnklkkieytnkithffkaknnkqqnnvth (SEQ ID NO. 403)kdsnenrkkkqkedkknpnklkkieytnkithffkaknnkqqnnvth (SEQ ID NO. 404)kkqkedkknpnklkkieytnkithffkaknnkqqnnvth (SEQ ID NO. 405)kqkedkknpnklkkieytnkithffkaknnkqqnnvth (SEQ ID NO. 406)kedkknpnklkkieytnkithffkaknnkqqnnvth (SEQ ID NO. 407)knpnklkkieytnkithffkaknnkqqnnvth (SEQ ID NO. 408)kkieytnkithffkaknnkqqnnvth (SEQ ID NO. 409) kieytnkithffkaknnkqqnnvth(SEQ ID NO. 410) kithffkaknnkqqnnvth (SEQ ID NO. 411)hknnedikndnskdikndnskdikndnskdikndnnedikndnskdik (SEQ ID NO. 412)hknnedikndnskdikndnskdikndnskdikndnnedikndnsk (SEQ ID NO. 413)hknnedikndnskdikndnskdikndnskdikndnnedik (SEQ ID NO. 414)hknnedikndnskdikndnskdikndnskdik (SEQ ID NO. 415)hknnedikndnskdikndnskdikndnsk (SEQ ID NO. 416) hknnedikndnskdikndnskdik(SEQ ID NO. 417) hknnedikndnskdikndnsk (SEQ lID NO. 418)hknnedikndnskdik (SEQ ID NO. 419) hknnedik (SEQ ID NO. 420)kkyddlqnkynilnklknsleekneelkkyh (SEQ ID NO. 421)kyddlqnkynilnklknsleekneelkkyh (SEQ ID NO. 422) kynilnklknsleekneelkkyh(SEQ ID NO. 423) klknsleekneelkkyh (SEQ ID NO. 424) knsleekneelkkyh (SEQID NO. 425) kneelkkyh (SEQ ID NO. 426)hmgnnqdinenvynikpqefkeeeeedismvntkk (SEQ ID NO. 427) knsnelkrindnffklh(SEQ ID NO. 428) kpclykkckisqclykkckisqvwwcmpvkdtfntyernnvlnskienniekiph(SEQ ID NO. 429) hinneytnknpkncllykneernyndnnikdyinsmnfkk (SEQ ID NO.430) hinneytnknpkncllykneernyndnnikdyinsmnfk (SEQ ID NO. 431)hinneytnknpkncllyk (SEQ ID NO. 432) knktnqskgvkgeyekkketngh (SEQ ID NO.433) ktnqskgvkgeyekkketngh (SEQ ID NO. 434) kgvkgeyekkketngh (SEQ ID NO.435) kgeyekkketngh (SEQ ID NO. 436) ksgmytnegnkscecsykkkssssnkvh (SEQ IDNO. 437) kscecsykkkssssnkvh (SEQ ID NO. 438) kkkssssnkvh (SEQ ID NO.439) kkssssnkvh (SEQ ID NO. 440) kssssnkvh (SEQ ID NO. 441)himlksgmytnegnkscecsykkkssssnk (SEQ ID NO. 442) himlksgmytnegnkscecsykkk(SEQ ID NO. 443) himlksgmytnegnkscecsykk (SEQ ID NO. 444)himlksgmytnegnkscecsyk (SEQ ID NO. 445)kplaklrkrektqinktkyergdviidnteiqkiiirdyhetlnvhkldh (SEQ ID NO. 446)krektqinktkyergdviidnteiqkiiirdyhetlnvhkldh (SEQ ID NO. 447)ktqinktkyergdviidnteiqkiiirdyhetlnvhkldh (SEQ ID NO. 448)kplaklrkrektqinktkyergdviidnteiqkiiirdyhetlnvh (SEQ ID NO. 449)kplaklrkrektqinktkyergdviidnteiqkiiirdyh (SEQ ID NO. 450)klrkrektqinktkyergdviidnteiqkiiirdyh (SEQ ID NO. 451)krektqinktkyergdviidnteiqkiiirdyh (SEQ ID NO. 452)ktqinktkyergdviidnteiqkiiirdyh (SEQ ID NO. 453)kkdkekkkdsnenrkkkqkedkknpndnklkkieytnkith (SEQ ID NO. 454)kdkekkkdsnenrkkkqkedkknpndnklkkieytnkith (SEQ ID NO. 455)kekkkdsnenrkkkqkedkknpndnklkkieytnkith (SEQ ID NO. 456)kkkdsnenrkkkqkedkknpndnklkkieytnkith (SEQ ID NO. 457)kkdsnenrkkkqkedkknpndnklkkieytnkith (SEQ ID NO. 458)kdsnenrkkkqkedkknpndnklkkieytnkith (SEQ ID NO. 459)kkkqkedkknpndnklkkieytnkith (SEQ ID NO. 460) kkqkedkknpndnklkkieytnkith(SEQ ID NO. 461) kqkedkknpndnklkkieytnkith (SEQ ID NO. 462)kedkknpndnklkkieytnkith (SEQ ID NO. 463) kknpndnklkkieytnkith (SEQ IDNO. 464) knpndnklkkieytnkith (SEQ ID NO. 465) klkkieytnkith (SEQ ID NO.466) kkieytnkith (SEQ ID NO. 467) kieytnkith (SEQ ID NO. 468)hgqikiedvnnenfnneqmknkyndeekmdiskskslksdflek (SEQ ID NO. 469)hgqikiedvnnenfnneqmknkyndeekmdiskskslk (SEQ ID NO. 470)hgqikiedvnnenfnneqmknkyndeekmdisksk (SEQ ID NO. 471)hgqikiedvnnenfnneqmknkyndeekmdisk (SEQ ID NO. 472)kkyddlqnkynilnklknsleekneelkkyh (SEQ ID NO. 473)kyddlqnkynilnklknsleekneelkkyh (SEQ ID NO. 474) kynilnklknsleekneelkkyh(SEQ ID NO. 475) klknsleekneelkkyh (SEQ ID NO. 476) knsleekneelkkyh (SEQID NO. 477) kneelkkyh (SEQ ID NO. 478)hmgnnqdinenvynikpqefkeeeeedismvntkkcddiqenik (SEQ ID NO. 479)ktnlyniynnknddkdnildnenreglylcdvmknsnelkrindnffklh (SEQ ID NO. 480)knsnelkrindnffklh (SEQ ID NO. 481) krindnffklh (SEQ ID NO. 482)hinneytnknpkncllykneernyndnnikdyinsmnfkk (SEQ ID NO. 483)hinneytnknpkncllykneernyndnnikdyinsmnfk (SEQ ID NO. 484)hinneytnknpkncllyk (SEQ ID NO. 485)kpclykkckisqvwwcmpvkdtfntyernnvlnskienniekiph (SEQ ID NO. 486)kckisqvwwcmpvkdtfntyernnvlnskienniekiph (SEQ ID NO. 487) kienniekiph(SEQ ID NO. 488) knktngskgvkgeyekkketngh (SEQ ID NO. 489)ktngskgvkgeyekkketngh (SEQ ID NO. 490) kgvkgeyekkketngh (SEQ ID NO. 491)kgeyekkketngh (SEQ ID NO. 492)ktiekinkskswffeeldeidkplaklrkrektqinktkyergdviidnteiqkiirdyh (SEQ ID NO.493) kinkskswffeeldeidkplaklrkrektqinktkyergdviidnteiqkiirdyh (SEQ IDNO. 494) kplaklrkrektqinktkyergdviidnteiqkiirdyh (SEQ ID NO. 495)himlksqmytnegnkscecsykkkssssnkvh (SEQ ID NO. 496)klrkrektqinktkyergdviidnteiqkiirdyh (SEQ ID NO. 497)krektqinktkyergdviidnteiqkiirdyh (SEQ ID NO. 498)ktqinktkyergdviidnteiqkiirdyh (SEQ ID NO. 499)kplaklrkrektqinktkyergdviidnteiqkiirdyhtlnvhkldh (SEQ ID NO. 500)klrkrektqinktkyergdviidnteiqkiirdyhtlnvhkldh (SEQ ID NO. 501)krektqinktkyergdviidnteiqkiirdyhtlnvhkldh(SEQ ID NO. 502)ktqinktkyergdviidnteiqkiirdyhtlnvhkldh (SEQ ID NO. 503)kplaklrkrektqinktkyergdviidnteiqkiirdyhtlnvh (SEQ ID NO. 504)klrkrektqinktkyergdviidnteiqkiirdyhtlnvh (SEQ ID NO. 505)krektqinktkyergdviidnteiqkiirdyhtlnvh (SEQ ID NO. 506)ktqinktkyergdviidnteiqkiirdyhtlnvh (SEQ ID NO. 507)himlksqmytnegnkscecsykkkssssnkvh (SEQ ID NO. 508)ksqmytnegnkscecsykkkssssnkvh (SEQ ID NO. 509) kscecsykkkssssnkvh (SEQ IDNO. 510) kkkssssnkvh (SEQ ID NO. 511) kkssssnkvh (SEQ ID NO. 512)kssssnkvh (SEQ ID NO. 513) himlksqmytnegnkscecsykkkssssnk (SEQ ID NO.514) himlksqmytnegnkscecsykkk (SEQ ID NO. 515) himlksqmytnegnkscecsykk(SEQ ID NO. 516) himlksqmytnegnkscecsyk (SEQ ID NO. 517)hnnhniqiykdkrinfmnphkvmyhdnmsknertek (SEQ ID NO. 518)hnnhniqiykdkrinfmnphkvmyhdnmsk (SEQ ID NO. 519) hnnhniqiykdkrinfmnphk(SEQ ID NO. 520) hkvmyhdnmsknertek (SEQ ID NO. 521) hkvmyhdnmsk (SEQ IDNO. 522)

Replikins in Structural Proteins

[0356] It has also been determined that some structural proteins includeReplikin structures. Structural proteins are molecules involved intissue and organ support, such as collagen in skin and connective tissueand in membrane structures, for example amyloid A4 precursor protein(APP) in brain. Overproduction of these proteins is associated withdisease; specifically, scleroderma in the case of overproduction ofcollagen in skin (Table 9) and Alzheimer's Disease in the case ofoverproduction of APP in the brain (Table 10).

[0357] The association of scleroderma and malignancy has been a sourceof controversy during recent years. Several mechanisms ofinterrelationship have been suggested in earlier reports. Recentlong-term studies suggest an increased association-ratio of sclerodermaand malignancy. However, the underlying mechanisms remain elusive.(Wenzel, J. Eur. J. Dermatol. 20002 May-Jun; 12(3): 296-300).

[0358] Several proteins concerned with the excessive production ofproteins in scleroderma have been found to contain Replikin structures.Thus, these provide further examples of unrecognized targets forinhibition or cessation of excessive collagen production. Table 9provides a list of proteins in scleroderma and the associated Replikins.

[0359] The APP protein is the source of the amyloid beta A4 protein,which in excessive amounts forms placques in the extracellular spaces inthe brain, producing toxic effects associated with nerve cell loss inAlzheimer's Disease. Most studies to date have focused on the inabilityto clear the excessive deposits of A4, but have not considered that,rather than a waste clearance problem, this may actually be a problem ofoverproduction of the precursor protein APP. The high concentration ofthe Replikins in APP (3.3 Replikins per 100 amino acids) stronglysuggest that overproduction may well be the cause of Alzheimer's Disease(Table 10). Therefore, the Replikins contained in Table 10 can beblocked or inhibited by the same methods as illustrated in detail forthe glioma Replikin. TABLE 9 Proteins overproduced in scleroderma andassociated Replikins: PMC1 HUMAN:hreictiqssggimllkdqvlrcskiagvkvaeitelilk (SEQ ID NO. 523)hreictiqssggimllkdqvlresk (SEQ ID NO. 524) 34KD nucleolar sclerodermaantigen: hreictiqssggimllkdqvlrcskiagvkvaeiteliklkalendqk (SEQ ID NO.525) hreictiqssggimllkdqvlrcskiagvkvaeitelilk (SEQ ID NO. 526)Fibrillarin: kkmqqenmkqpeqltlepyerdh (SEQ ID NO. 527)kmqqenmkpqeqltlepyerdh (SEQ ID NO. 528) SPOP HUMAN:hemeeskknrveindvepevfkemmcfiytgkapnldk (SEQ ID NO. 529)hemeeskknrveindvepevfkemmcfiytgk (SEQ ID NO. 530) Centromere protein C:khgelkvyk (SEQ ID NO. 531) klilgpqeekgkqh (SEQ ID NO. 532) hnrihhk (SEQID NO. 533) hhnssrkstkktnqssk (SEQ ID NO. 534) hnssrkstkktnqssk (SEQ IDNO. 535) khhnilpktlandkhshkph (SEQ ID NO. 536) hhnilpktlandkhshk (SEQ IDNO. 537) hnilpktlandkhshk (SEQ ID NO. 538) hnilpktlandk (SEQ ID NO. 539)kntpdskkissrnindhh (SEQ ID NO. 540) kntpdskkissrnindh (SEQ ID NO. 541)kdtciqspskecqkshpksvpvsskkk (SEQ ID NO. 542) kdtciqspskecqkshpksvpvsskk(SEQ ID NO. 543) hpksvpvsskkk (SEQ ID NO. 544) hpksvpvsskk (SEQ ID NO.545) hpksvpvssk (SEQ ID NO. 546) Factor CTCBF, KU antigen:kalqekveikqlnh (SEQ ID NO. 547)ktlfplieakkdqvtageifgdnhedgptakklktegggah (SEQ ID NO. 548)ktlfplieakkkdqvtageifqdnb (SEQ ID NO. 549) klcvfkkierhsih (SEQ ID NO.550) klcvfkkierh (SEQ ID NO. 551) kgpsfplkgiteqqkegleivk (SEQ ID NO.552) hgpsfplkgiteqqk (SEQ ID NO. 553) ATP synthase subunit 6:htllkilstflfk (SEQ ID NO. 554) hllgnndknllpsk (SEQ ID NO. 555) FBRLnuclear protein: hrhegvficrgkedalvtk (SEQ ID NO. 556) hegvficrgkedalvtk(SEQ ID NO. 557) hsggnrgrgrggkrghqsgk (SEQ ID NO. 558) krgnqsgknvmveph(SEQ ID NO. 559) krgnqsgknvmvephrh (SEQ ID NO. 560)kkmqqenmkpqeqltlepyerdh (SEQ ID NO. 561) kmqqenmkpqeqltlepyerdh (SEQ IDNO. 562) HP1Hs-alpha protein: haypedaenkeketak (SEQ ID NO. 563)keanvkcpqiviafyeerltwh (SEQ ID NO. 564) kvldrrvvkgqveyllkwkgfseeh (SEQID NO. 565) kgqveyllkwkgfseeh (SEQ ID NO. 566) FM/Scl nucleolar protein:ksevaagvkksglpsaerlenvlfgphdcsh (SEQ ID NO. 567)ksevaagvkksgplpsaerlenvlfgph (SEQ ID NO. 568)kaaeygkkaksetfrllhakniirpqlk (SEQ ID NO. 569) kaaeygkkaksetfrllhak (SEQID NO. 570) ksetfrllhak (SEQ ID NO. 571) hakniirpqlk (SEQ ID NO. 572)hmnlkiaeelpk (SEQ ID NO. 573) hsldhllklycnvdsnk (SEQ ID NO. 574)hllklycnvdsnk (SEQ ID NO. 575)

[0360] TABLE 10 Amyloid beta A4 precursor protein (APP) Replikins:kakerleakh (SEQ ID NO. 576) kdrqhtlk (SEQ ID NO. 577) kdrqhtlkh (SEQ IDNO. 578) ketcsekstnlh (SEQ ID NO. 579) kteeisevkmdaefgh (SEQ ID NO. 580)kteeisevkmdaefghdsgfevrh (SEQ ID NO. 581) kkyvraeqkdrqhtlkh (SEQ ID NO.582) kyvraeqkdrqhtlkh (SEQ ID NO. 583) kkyvraeqkdrqh (SEQ ID NO. 584)kyvraeqkdrqht (SEQ ID NO. 585) hhvfnmlkkyvraeqk (SEQ ID NO. 586)hvfnmlkkyvraeqk (SEQ ID NO. 587) hhvfnmlkkyvraeqkdrqhtlkh (SEQ ID NO.588) hvfnmlkkyvraeqkdrqhtlkh (SEQ ID NO. 589) hahfqkakerleakh (SEQ IDNO. 590) hahfqkakerleak (SEQ ID NO. 591) hfqkakerleak (SEQ ID NO. 592)hqermdvcethlhwhtvaketcsekstnlh (SEQ ID NO. 593)hqermdvcethlhwhtvaketcsek (SEQ ID NO. 594) hwhtvaketcsek (SEQ ID NO.595) htvaketcsek (SEQ ID NO. 596) hlhwhtvaketcsek (SEQ ID NO. 597)hmnvqngkwesdpsgtktcigtk (SEQ ID NO. 598) hmnvqngkwesdpsgtk (SEQ ID NO.599)

Passive Immunity

[0361] In another embodiment of the invention, isolated Replikinpeptides may be used to generate antibodies, which may be used, forexample to provide passive immunity in an individual. Passive immunityto the strain of influenza identified by the method of the invention tobe the most likely cause of future influenza infections may be obtainedby administering antibodies to Replikin sequences of the identifiedstrain of influenza virus to patients in need. Similarly, passiveimmunity to malaria may be obtained by administering antibodies toPlasmodium falciparum Replikin(s).

[0362] Various procedures known in the art may be used for theproduction of antibodies to Replikin sequences. Such antibodies includebut are not limited to polyclonal, monoclonal, chimeric, humanized,single chain, Fab fragments and fragments produced by an Fab expressionlibrary. Antibodies that are linked to a cytotoxic agent may also begenerated. Antibodies may also be administered in combination with anantiviral agent. Furthermore, combinations of antibodies to differentReplikins may be administered as an antibody cocktail.

[0363] For the production of antibodies, various host animals or plantsmay be immunized by injection with a Replikin peptide or a combinationof Replikin peptides, including but not limited to rabbits, mice, rats,and larger mammals.

[0364] Monoclonal antibodies to Replikins may be prepared by using anytechnique that provides for the production of antibody molecules. Theseinclude but are not limited to the hybridoma technique originallydescribed by Kohler and Milstein, (Nature, 1975, 256:495-497), the humanB-cell hybridoma technique (Kosbor et al., 1983, Immunology Today,4:72), and the EBV hybridoma technique (Cole et al., MonoclonalAntibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Inaddition, techniques developed for the production of chimeric antibodies(Morrison et al., 1984, Proc. Nat. Acad. Sci USA, 81:6851-6855) or othertechniques may be used. Alternatively, techniques described for theproduction of single chain antibodies (U.S. Pat. No. 4,946,778) can beadapted to produce Replikin-specific single chain antibodies.

[0365] Particularly useful antibodies of the invention are those thatspecifically bind to Replikin sequences contained in peptides and/orpolypeptides of influenza virus. For example, antibodies to any ofpeptides observed to be present in an emerging or re-emerging strain ofinfluenza virus and combinations of such antibodies are useful in thetreatment and/or prevention of influenza. Similarly, antibodies to anyReplikins present on malaria antigens and combinations of suchantibodies are useful in the prevention and treatment of malaria.

[0366] Antibody fragments which contain binding sites for a Replikin maybe generated by known techniques. For example, such fragments includebut are not limited to F(ab′)2 fragments which can be produced by pepsindigestion of the antibody molecules and the Fab fragments that can begenerated by reducing the disulfide bridges of the F(ab′)2 fragments.Alternatively, Fab expression libraries can be generated (Huse et al.,1989, Science, 246:1275-1281) to allow rapid and easy identification ofmonoclonal Fab fragments with the desired specificity.

[0367] The fact that antimalignin antibody is increased in concentrationin human malignancy regardless of cancer cell type (FIG. 5), and thatthis antibody binds to malignant cells regardless of cell type now maybe explained by the presence of the Replikin structures herein found tobe present in most malignancies (FIG. 1 and Table 2). Population studieshave shown that antimalignin antibody increases in concentration inhealthy adults with age, and more so in high-risk families, as thefrequency of cancer increases. An additional two-fold or greaterantibody increase which occurs in early malignancy has beenindependently confirmed with a sensitivity of 97% in breast cancers 1-10mm in size. Shown to localize preferentially in malignant cells in vivo,histochemically the antibody does not bind to normal cells butselectively binds to (FIG. 4a, b) and is highly cytotoxic to transformedcells in vitro (FIGS. 4c-f). Since in these examples the same antibodyis bound by several cell types, that is, brain glioma, hematopoieticcells (leukemia), and small cell carcinoma of lung, malignant Replikinclass unity is again demonstrated.

[0368] Antimalignin does not increase with benign proliferation, butspecifically increases only with malignant transformation andreplication in breast in vivo and returns from elevated to normal valuesupon elimination of malignant cells (FIG. 5). Antimalignin antibodyconcentration has been shown to relate quantitatively to the survival ofcancer patients, that is, the more antibody, the longer the survival.Taken together, these results suggest that anti-Replikin antibodies maybe a part of a mechanism of control of cell transformation andreplication. Augmentation of this immune response may be useful in thecontrol of replication, either actively with synthetic Replikins asvaccines, or passively by the administration of anti-Replikinantibodies, or by the introduction of non-immune based organic agents,such as for example, carbohydrates, lipids and the like, which aresimilarly designed to target the Replikin specifically.

[0369] In another embodiment of the invention, immune serum containingantibodies to one or more Replikins obtained from an individual exposedto one or more Replikins may be used to induce passive immunity inanother individual or animal. Immune serum may be administered via i.v.to a subject in need of treatment. Passive immunity also can be achievedby injecting a recipient with preformed antibodies to one or moreReplikins. Passive immunization may be used to provide immediateprotection to individuals who have been exposed to an infectiousorganism. Administration of immune serum or preformed antibodies isroutine and the skilled practitioner can readily ascertain the amount ofserum or antibodies needed to achieve the desired effect.

Synthetic Replikin Vaccine (Active Immunity)

[0370] Synthetic Replikin vaccines, based on Replikins such as theglioma Replikin (SEQ ID NO.: 1) “kagvaflhkk” or the hepatitis C Replikin(SEQ ID NO.: 18) “hyppkpgcivpak”, or HIV Replikins such as (SEQ ID NO.:5) “kcfncgkegh” or (SEQ ID NO.: 6) “kvylawvpahk” or preferably, aninfluenza vaccine based on conserved and/or emerging or re-emergingReplikin(s) over a given time period may be used to augment antibodyconcentration in order to lyse the respective virus infected cells andrelease virus extracellularly where chemical treatment can then beeffective. Similarly, a malaria vaccine, based on Replikins observed inPlasmodium falciparum malaria antigens on the merozoite surface orwithin the parasitophorous vacuole, for example, can be used to generatecytotoxic antibodies to malaria.

[0371] Recognin and/or Replikin peptides may be administered to asubject to induce the immune system of the subject to produceanti-Replikin antibodies. Generally, a 0.5 to about 2 mg dosage,preferably a 1 mg dosage of each peptide is administered to the subjectto induce an immune response. Subsequent dosages may be administered ifdesired.

[0372] The Replikin sequence structure is associated with the functionof replication. Thus, whether the Replikins of this invention are usedfor targeting sequences that contain Replikins for the purpose ofdiagnostic identification, promoting replication, or inhibiting orattacking replication, for example, the structure-function relationshipof the Replikin is fundamental.

[0373] It is preferable to utilize only the specific Replikin structurewhen seeking to induce antibodies that will recognize and attach to theReplikin fragment and thereby cause destruction of the cell. Even thoughthe larger protein sequence may be known in the art as having a“replication associated function,” vaccines using the larger proteinoften have failed or proven ineffective.

[0374] Although the present inventors do not wish to be held to a singletheory, the studies herein suggest that the prior art vaccines areineffective because they are based on the use of the larger proteinsequence. The larger protein sequence invariably has one or moreepitopes (independent antigenic sequences that can induce specificantibody formation); Replikin structures usually comprise one of thesepotential epitopes. The presence of other epitopes within the largerprotein may interfere with adequate formation of antibodies to theReplikin, by “flooding” the immune system with irrelevant antigenicstimuli that may preempt the Replikin antigens, See, e.g., Webster, R.G., J. Immunol., 97(2):177-183 (1966); and Webster et al., J. Infect.Dis., 134:48-58, 1976; Klenerman et al, Nature 394:421-422 (1998) for adiscussion of this well-known phenomenon of antigenic primacy wherebythe first peptide epitope presented and recognized by the immune systemsubsequently prevails and antibodies are made to it even though otherpeptide epitopes are presented at the same time. This is another reasonthat, in a vaccine formulation, it is important to present the constantReplikin peptide to the immune system first, before presenting otherepitopes from the organism so that the Replikin is not preempted butlodged in immunological memory.

[0375] The formation of an antibody to a non-Replikin epitope may allowbinding to the cell, but not necessarily lead to cell destruction. Thepresence of structural “decoys” on the C-termini of malaria proteins isanother aspect of this ability of other epitopes to interfere withbinding of effective anti-Replikin antibodies, since the decoy epitopeshave many lysine residues, but no histidine residues. Thus, decoyepitopes may bind anti-Replikin antibodies, but may keep the antibodiesaway from histidine-bound respiratory enzymes. Treatment may thereforebe most efficacious in two stages: 1) proteases to hydrolize decoys,then; 2) anti-Replikin antibodies or other anti-Replikin agents.

[0376] It is well known in the art that in the course of antibodyproduction against a “foreign” protein, the protein is first hydrolyzedinto smaller fragments. Usually fragments containing from about six toten amino acids are selected for antibody formation. Thus, if hydrolysisof a protein does not result in Replikin-containing fragments,anti-Replikin antibodies will not be produced. In this regard, it isinteresting that Replikins contain lysine residues located six to tenamino acids apart, since lysine residues are known to bind to membranes.

[0377] Furthermore, Replikin sequences contain at least one histidineresidue. Histidine is frequently involved in binding to redox centers.Thus, an antibody that specifically recognizes a Replikin sequence has abetter chance of inactivating or destroying the cell in which theReplikin is located, as seen with anti-malignin antibody, which isperhaps the most cytotoxic anti-cancer antibody yet described, beingactive at picograms per cell.

[0378] One of the reasons that vaccines directed towards a particularprotein antigen of a disease causing agent have not been fully effectivein providing protection against the disease (such as foot and mouthvaccine which has been developed against the VP 1 protein or largesegments of the VP 1 protein) is that the best antibodies have not beenproduced, that is—it is likey that the antibodies to the Replikins havenot been produced. Replikins have not been produced. That is, eitherepitopes other than Replikins present in the larger protein fragmentsmay interfere according to the phenomenon of antigenic primacy referredto above, and/or because the hydrolysis of larger protein sequences intosmaller sequences for processing to produce antibodies results in lossof integrity of any Replikin structure that is present, e.g., theReplikin is cut in two and/or the histidine residue is lost in thehydrolytic processing. The present studies suggest that for an effectivevaccine to be produced, the Replikin sequences, and no other epitope,should be used as the vaccine. For example, a vaccine of the inventioncan be generated using any one of the Replikin peptides identified bythe three point recognition system.

[0379] Particularly preferred peptides—for example—an influenza vaccineinclude peptides that have been demonstrated to be conserved over aperiod of one or more years, preferably about three years or more,and/or which are present in a strain of influenza virus shown to havethe highest increase in concentration of Replikins relative to Replikinconcentration in other influenza virus strains, e.g., an emergingstrain. The increase in Replikin concentration preferably occurs over aperiod of at least about six months to one year, preferably at leastabout two years or more, and most preferably about three years or more.Among the preferred Replikin peptides for use in an influenza virusvaccine are those Replikins observed to “re-emerge” after an absencefrom the hemagglutinin amino acid sequence for one or more years.

[0380] The Replikin peptides of the invention, alone or in variouscombinations are administered to a subject, preferably by i.v. orintramuscular injection, in order to stimulate the immune system of thesubject to produce antibodies to the peptide. Generally the dosage ofpeptides is in the range of from about 0.1 μg to about 10 mg, preferablyabout 10 μg to about 1 mg, and most preferably about 50 μg to about 500ug. The skilled practitioner can readily determine the dosage and numberof dosages needed to produce an effective immune response.

Quantitative Measurement Early Response(S) to Replikin Vaccines

[0381] The ability to measure quantitatively the early specific antibodyresponse in days or a few weeks to a Replikin vaccine is a majorpractical advantage over other vaccines for which only a clinicalresponse months or years later can be measured.

Adjuvants

[0382] Various adjuvants may be used to enhance the immunologicalresponse, depending on the host species, including but not limited toFreund's (complete and incomplete), mineral gels, such as aluminumhydroxide, surface active substances such as lysolecithin, pluronicpolyols, polyanions, peptides, oil emulsions, key limpet hemocyanin,dintrophenol, and potentially useful human adjuvants such as BCG andCorynebacterium parvum.

Replikin Nucleotide Sequences

[0383] Replikin DNA or RNA may have a number of uses for the diagnosisof diseases resulting from infection with a virus, bacterium or otherReplikin encoding agent. For example, Replikin nucleotide sequences maybe used in hybridization assays of biopsied tissue or blood, e.g.,Southern or Northern analysis, including in situ hybridization assays,to diagnose the presence of a particular organism in a tissue sample oran environmental sample, for example. The present invention alsocontemplates kits containing antibodies specific for particularReplikins that are present in a particular pathogen of interest, orcontaining nucleic acid molecules (sense or antisense) that hybridizespecifically to a particular Replikin, and optionally, various buffersand/or reagents needed for diagnosis.

[0384] Also within the scope of the invention are oligoribonucleotidesequences, that include antisense RNA and DNA molecules and ribozymesthat function to inhibit the translation of Replikin- orrecognin-containing mRNA. Both antisense RNA and DNA molecules andribozymes may be prepared by any method known in the art. The antisensemolecules can be incorporated into a wide variety of vectors fordelivery to a subject. The skilled practitioner can readily determinethe best route of delivery, although generally i.v. or i.m. delivery isroutine. The dosage amount is also readily ascertainable.

[0385] Particularly preferred antisense nucleic acid molecules are thosethat are complementary to a Replikin sequence contained in a mRNAencoding, for example, an influenza virus polypeptide, wherein theReplikin sequence comprises from 7 to about 50 amino acids including:

[0386] (1) at least one lysine residue located six to ten residues froma second lysine residue;

[0387] (2) at least one histidine residue; and

[0388] (3) at least 6% lysine residues.

[0389] More preferred are antisense nucleic acid molecules that arecomplementary to a Replikin present in the coding strand of the gene orto the mRNA encoding the influenza virus hemagglutinin protein, whereinthe antisense nucleic acid molecule is complementary to a nucleotidesequence encoding a Replikin that has been demonstrated to be conservedover a period of six months to one or more years and/or which arepresent in a strain of influenza virus shown to have an increase inconcentration of Replikins relative to Replikin concentration in otherinfluenza virus strains. The increase in Replikin concentrationpreferably occurs over a period of at least six months, preferably aboutone year, most preferably about two or three years or more.

[0390] Similarly, antisense nucleic acid molecules that arecomplementary to mRNA those that are complementary to a mRNA encodingbacterial Replikins comprising a Replikin sequence of from 7 to about 50amino acids including:

[0391] (1) at least one lysine residue located six to ten residues froma second lysine residue;

[0392] (2) at least one histidine residue; and

[0393] (3) at least 6% lysine residues.

[0394] More preferred are antisense nucleic acid molecules that arecomplementary to the coding strand of the gene or to the mRNA encoding aprotein of the bacteria.

Diagnostic Applications

[0395] For organisms such as diatom plankton, foot and mouth diseasevirus, tomato leaf curl gemini virus, hepatitis B and C, HIV, influenzavirus and malignant cells, identified constituent Replikins are usefulas vaccines, and also may be usefully targeted for diagnostic purposes.For example, blood collected for transfusions may be screened forcontamination of organisms, such as HIV, by screening for the presenceof Replikins shown to be specific for the contamination organism. Also,screening for Replikin structures specific for a particular pathologicalorganism leads to diagnostic detection of the organism in body tissue orin the environment.

Replikin Stimulation of Growth

[0396] In another embodiment of the invention, Replikin structures areused to increase the replication rate of cells, tissues or organs. Amethod is available to increase replication rates by the addition ofspecific Replikin structures for other cells, tissues or organs that itis desired to replicate more rapidly, together with or withoutappropriate stimulae to cell division know in the art for said cells,tissues or organs to increase the rate of replication and yield. Thismay be accomplished, for example, by methods known in the art, bymodifying or transforming a gene encoding for or associated with aprotein or enzyme having a replication function in the organism with atleast one Replikin structure.

[0397] In another aspect of the invention, Replikin structures are usedto increase the replication of organisms. The present inventiondemonstrates that in influenza virus, for example, increased replicationassociated with epidemics is associated with increased concentration ofReplikins. The increase is due to 1) the reappearance of particularReplikin structures, which were present in previous years, but whichthen disappeared for one or more years; and/or 2) by the appearance ofnew Replikin compositions. In addition, in malaria Replikins, repetitionof the same Replikin in a single protein occurs.

[0398] Thus, the present invention provides methods and compositions forincreasing the replication of organisms. Similarly, in the manner thatReplikins of different organisms can be targeted to inhibit replicationof any organism, Replikins can be used to increase the replication ofany organism. For example, production of rice, maize, and wheat crops,which are critical to feeding large populations in the world, can beimproved, for example, by increasing the concentration (number ofReplikins/100 amino acid residues) of any particular strain of rice.

[0399] As an example, in the Oryza sativa strain of rice, catalaseisolated from immature seeds was observed to contain the followingdifferent Replikins within the 491 amino acid sequence of the protein:

[0400] kfpdvihafkpnprsh (SEQ ID NO. 625)

[0401] kfpdvihafk (SEQ ID NO. 626)

[0402] karyvkfhwk (SEQ ID NO. 627)

[0403] hpkvspelraiwvnylsqedeslgvkianlnvk (SEQ ID NO. 628)

[0404] hrdeevdyypsrhaplrhapptpitprpvvgrrqkatihkqndfk (SEQ ID NO. 629)

[0405] katihkqndfk (SEQ ID NO. 630)

[0406] happtpitprpvvgrrqkatihkqndfk (SEQ ID NO. 631)

[0407] kfrpsssfdtkttttnagapvwndnealtvgprgpilledyhliekvah (SEQ ID NO.632)

[0408] kfrpsssfdtkttttnagapvwndnealtvgprgpilledyn (SEQ ID NO. 633)

[0409] Thus, by using recombinant gene cloning techniques well known inthe art, the concentration of Replikin structures in an organism, suchas a food crop plant, can be increased, which will promote increasedreplication of the organism. For example, inserting additional Replikinsequences like the Replikins identified above into the Oryza sativacatalase gene by methods well know in the art will promotethisorganism's replication.

[0410] Similarly, in the NBS-LRR protein of Oryza sativa (japonicacultivar group), the following Replikins were found:

[0411] kvkahfqkh (SEQ ID NO. 634)

[0412] kvkahfqk (SEQ ID NO. 635)

[0413] kdyeidkddlih (SEQ ID NO. 636)

[0414] hmkqcfafcavfpkdyeidk (SEQ ID NO. 637)

[0415] hmkqcfafcavfpk (SEQ ID NO. 638)

[0416] hvfwelvwrsffqnvkqigsifqrkvyrygqsdvttskihdlmhdlavh (SEQ ID NO.639)

[0417] kqigsifqrkvrygpsdvttskihdlmhdlavh (SEQ ID NO. 640)

[0418] kqigsifqrkvyrygpsdvttskihdlmh (SEQ ID NO. 641)

[0419] kqigsifqrkvyrygqsdvttskih (SEQ ID NO. 642)

[0420] Further, for aspartic proteinase oryzasin 1 precursor protein,the following Replikins were found:

[0421] khgvsagik (SEQ ID NO. 643)

[0422] htvfdygkmrvgfak (SEQ ID NO. 644)

[0423] hsryksgqsstyqkngk (SEQ ID NO. 645)

[0424] Similarly, in the MADS-box protein FDRMADS3 transcription factorof Oryza sativa (indica cultivar-group), the following Replikins werefound:

[0425] kqeamvlkqeinllqkglryiygnraneh (SEQ ID NO. 646)

[0426] kqeinllqkglryiygnraneh (SEQ ID NO. 647)

[0427] kskegmlkaaneilqekiveqnglidvgmmvadqqngh (SEQ ID NO. 648)

[0428] kaaneilqekiveqnglidvgmmvadqqngh (SEQ ID NO. 649)

[0429] Similarly, in LONI MAIZE (ATP-binding redox associated Hydrolase;Serine protease; Multigene family; Mitochondrion), the followingReplikins were found:

[0430] kylaahrygik (SEQ ID NO. 650)

[0431] klkiamkhlipryleqh (SEQ ID NO. 651)

[0432] klkiamkh (SEQ ID NO. 652)

[0433] ktslassiakalnrkfirislggvkdeadirgh (SEQ ID NO. 653)

[0434] kalnrkfirislggvkdeadirgh (SEQ ID NO. 654)

[0435] kfirislggvkdeadirgh (SEQ ID NO. 655)

[0436] kvrlskatelvdrhlqsilvaekitqkvegqlsksqk (SEQ ID NO. 656)

[0437] hlqsilvaekitqkvegglsksqk (SEQ ID NO. 657)

[0438] kvrlskatelvdrh (SEQ ID NO. 658)

[0439] kvggsavesskqdtkngkepihwhskgvaaralh (SEQ ID NO. 659)

[0440] kvggsavesskqdtkngkepihwh (SEQ ID NO. 660)

[0441] kvggsavesskqdtkngkepih (SEQ ID NO. 661)

[0442] kqdtkngkepihwhskgvaaralh (SEQ ID NO. 662)

[0443] kqdtkngkepih (SEQ ID NO. 663)

[0444] Similarly, for Glyceraldehyde 3-phospate dehydrogenase A, achloroplast precursor, the following Replikins are found:

[0445] hrdlrraraaalnivptstgaakavslylpnlk (SEQ ID NO. 664)

[0446] kylddqkfgiikgtmttth (SEQ ID NO. 665)

[0447] hiqagakkylitapgk (SEQ ID NO. 666)

[0448] hgrgdaspldviaindtggvkqashllk (SEQ ID NO. 667)

[0449] kqashllk (SEQ ID NO. 697)

[0450] Further, examples of rust resistance-like protein RP1-4 (Zeamays) found include the following Replikins:

[0451] kvrrylskdysslkqlmtlmmdddiskhlqiiesgleeredkvwmkeniik (SEQ ID NO.668)

[0452] kvrrylskdysslkqlmtlmmdddiskh (SEQ ID NO. 669)

[0453] hlqiiesgleeredkvwmkeniik (SEQ ID NO. 670)

[0454] hdlreniimkaddlask (SEQ ID NO. 671)

[0455] hvqnlenvigkdealask (SEQ ID NO. 672)

[0456] kkqgyelrqlkdlnelggslh (SEQ ID NO. 673)

[0457] kqgyelrqlkdlnelggslh (SEQ ID NO. 674)

[0458] klylksrlkelilewssengmdamilh (SEQ ID NO. 675)

[0459] hlqllqlngmverlpnkvcnlsklrylrgykdqipnigk (SEQ ID NO. 676)

[0460] hlqllqlngmverlpnkvcnlskrylrgyk (SEQ ID NO. 677)

[0461] hlqllqlngmverlpnkvcnlsk (SEQ ID NO. 678)

[0462] hnsnklpksvgelk (SEQ ID NO. 679)

[0463] klpkvgelkh (SEQ ID NO. 680)

[0464] hlsvrvesmqkhkeiiyk (SEQ ID NO. 681)

[0465] khkeiiyk (SEQ ID NO. 682)

[0466] klrdilqesqkfllyldlalfkh (SEQ ID NO. 683)

[0467] hafsgaeikdqllrmklqdtaeeiakrlgqcplaakylgsrmcrrk (SEQ ID NO. 684)

[0468] hafsgaeikdqllrmk (SEQ ID NO. 685)

[0469] klqdtaeeiakrlgqclaakylgsrmcrrkdiaewkaadvwfeksh (SEQ ID NO. 686)

[0470] kylgsrmcrrkdiaewkaadvwfeksh (SEQ ID NO. 687)

[0471] kdiaewkaadvwfeksh (SEQ ID NO. 688)

[0472] kaadvwfeksh (SEQ ID NO. 689)

[0473] hvptttslptskvfgmsdrdrivkfllgktttaeasstk (SEQ ID NO. 690)

[0474] kailteakqlrdllglph (SEQ ID NO. 691)

[0475] kakaksgkgpllredessstattvmkpfl (SEQ ID NO. 692)

[0476] ksphrgkleswlrrlkeafydaedlldeh (SEQ ID NO. 693)

[0477] ksphrgkleswlrrlk (SEQ ID NO. 694)

[0478] hrgkleswlrrlk (SEQ ID NO. 695)

[0479] ksphrgk (SEQ ID NO. 696)

[0480] As discussed previously, the Replikin in wheat ubiquitinactivating enzyme E (SEQ ID Nos. 601-603) is conserved. Thisconservation of Replikin structure provides reliable targets forstimulation of plant growth.

[0481] The close relationship of Replikins to redox enzymes is alsoclearly indicated in this structure in wheat. Thus, this wheat ubiquitinactivating enzyme E activates ubiquitin by first adenylating with ATPits carboxy-terminal glycine residue and, thereafter, linking thisresidue to the side chain of a cysteine residue in E1 (SEQ ID NO. 603),yielding an ubiquitin-E1 thiolester and free AMP.

[0482] A further example of the relationship of wheat Replikins to redoxenzymes was also found in the PSABWheat Protein, Photosystem I P700chlorophyll A apoprotein A2 (PsaB) (PSI-B) isolated from bread Chinesespring wheat Chloroplast Triticum aestivum. This protein functions asfollows: PsaA and PsaB bind 9700, the primary electron donor ofphotosystem I (PSI), as well as the electron acceptors AO, Al, and FX.PSI functions as a plastocyanin/cytochrome c6-ferredoxin oxidoreductase.Cofactor P700 is a chlorophyll A dimer, A0 is chlorophyll A, A1 is aphylloquinone and FX is a 4Fe-4S iron-sulfur center. The subunit ApsaA/S heterodimer binds the P700 chlorophyll special pair andsubsequent electron acceptors. The PSI reaction center of higher plantsand algae is composed of one at least 11 subunits. This is an integralmembrane protein of the Chloroplast thylakoid membrane. The 4Fe-4Siron-sulfur “center” to which ‘h’ bind is critical; hence thesignificance of ‘h’ in Replikin structure. Next to bacterial Replikins,these wheat Replikins and plant Replikins are the most primitiveevolutionary illustrations of the importance of the Replikin structureto replication and the energy source needed for replication. This basicrelationship carries through algae, virus Replikins, bacteria, cancercells, and apparently all organisms with regard to replication.

[0483] Further examples of Replikins were found in the PSAB Wheatprotein, which is critical fox wheat growth. These include:

[0484] hlqpkwkpslswfknaesrlnhh (SEQ ID NO. 604)

[0485] hlqpkwkpslswfk (SEQ ID NO. 605)

[0486] kwkpslswfknaesrlnhh (SEQ ID NO. 606)

[0487] kwkpslswfknaesrlnh (SEQ ID NO. 607)

[0488] kpslswfknaesrlnhh (SEQ ID NO. 608)

[0489] kpslswfknaesrlnh (SEQ ID NO. 609)

[0490] hhaialglhtttlilvkgaldargsklmpdkk (SEQ ID NO. 610)

[0491] haialglhtttlilvkgaldargsklmpdkk (SEQ ID NO. 611)

[0492] hhaialglhtttlilvkgaldargsk (SEQ ID NO. 612)

[0493] haialglhtttlilvkgaldargsk (SEQ ID NO. 613)

[0494] htttlilvkgaldargsklmpdkk (SEQ ID NO. 614)

[0495] htttlilvkgaldargsklmpdk (SEQ ID NO. 615)

[0496] htttlilvkgaldargsk (SEQ ID NO. 616)

[0497] A further example of the relationship of wheat Replikins to redoxis provide in the PSAA_WHEAT Photosystem I 9700 chlorophyll A apoproteinA1, that include:

[0498] hhhlaiailfliaghmyrtnwgighglkdileahkgpftgqghk (SEQ ID NO. 617)

[0499] hhlaiailfliaghmyrtnwgighglkdileahkgpftgqghk (SEQ ID NO. 618)

[0500] hlaiailfliaghmyrtnwgighglkdileahkgpftgqghk (SEQ ID NO. 619)

[0501] hmyrtnwgighglkdileahkgpftgqghk (SEQ ID NO. 620)

[0502] hglkdileahkgpftgqghk (SEQ ID NO. 621)

[0503] hdileahkgpftgqghk (SEQ ID NO. 622)

[0504] hkgpftgqghk (SEQ ID NO. 623)

[0505] kgpftgqghk (SEQ ID NO. 624)

Computer Software for Identifying Replikins

[0506] The present invention also provides methods for identifyingReplikin sequences in an amino acid or nucleic acid sequence. Visualscanning of over four thousand sequences was performed in developing thepresent 3-point-recognition methods. However, data banks comprisingnucleotide and/or amino acid sequences can also be scanned by computerfor the presence of sequences meeting the 3 point recognitionrequirements.

[0507] According to another embodiment of the invention, three-pointrecognition methods described herein may be performed by a computer.FIG. 6 is a block diagram of a computer available for use with theforegoing embodiments of the present invention. The computer may includea processor, an input/output device and a memory storing executableprogram instructions representing the 3-point-recognition methods of theforegoing embodiments. The memory may include a static memory, volatilememory and/or a nonvolatile memory. The static memory conventionally maybe a read only memory (“ROM”) provided on a magnetic, or an electricalor optical storage medium. The volatile memory conventionally may be arandom accessmemory (“RAM”) and may be integrated as a cache within theprocessor or provided externally from the processor as a separateintegrated circuit. The non-volatile memory may be an electrical,magnetic or optical storage medium.

[0508] From a proteomic point of view the construction of a “3-pointrecognition” template based on the new glioma peptide sequence leddirectly to identification of a biology-wide class of proteins havingrelated structures and functions. The operation of the3-point-recognition method resembles identification by the use of a“keyword” search; but instead of using the exact spelling of the keyword“kagvaflhkk” (SEQ ID NO.: 1) as in a typical sequence homology search,or in the nucleotide specification of an amino acid, an abstraction ofthe keyword delimited by the “3-point-recognition” parameters is used.This delimited abstraction, although derived from a single relativelyshort amino acid sequence leads to identification of a class of proteinswith structures that are defined by the same specifications. Thatparticular functions, in this case transformation and replication, inaddition to structures, turn out also to be shared by members of theexposed class suggests that these structures and functions are related.Thus, from this newly identified short peptide sequence, a molecularrecognition ‘language’ has been formulated, which previously has notbeen described. Further, the sharing of immunological specificity bydiverse members of the class, as here demonstrated for the cancerReplikins, suggests that B cells and their product antibodies recognizeReplikins by means of a similar recognition language.

Other Uses of the Three Point Recognition Method

[0509] Since “3-point-recognition” is a proteomic method that specifiesa particular class of proteins, using three or more differentrecognition points for other peptides similarly should provide usefulinformation concerning other proteins classes. Further, the“3-point-recognition” method is applicable to other recognins, forexample to the TOLL ‘innate’ recognition of lipopolyssacharides oforganisms. The three point recognition method may also be modified toidentify other useful compounds of covalently linked organic molecules,including other covalently linked amino acids, nucleotides,carbohydrates, lipids or combinations thereof. In this embodiment of theinvention a sequence is screened for subsequences containing three ormore desired structural characteristics. In the case of screeningcompounds composed of covalently linked amino acids, lipids orcarbohydrates the subsequence of 7 to about 50 covalently linked unitsshould contain (1) at least one first amino acid, carbohydrate or lipidresidue located seven to ten residues from a second of the first aminoacid, carbohydrate or lipid residue; (2) encoding at least one secondamino acid, lipid or carbohydrate residue; and (3) at least 6% of thefirst amino acid, carbohydrate or lipid residue. In the case ofscreening nucleotide sequences, the subsequence of about 21 to about 150nucleotides should contain (1) at least one codon encoding a first aminoacid located within eighteen to thirty nucleotides from a second codonencoding the first amino acid residue; (2) at least one second aminoacid residue; and (3) encodes at least 6% of said first amino acidresidue.

[0510] Several embodiments of the present invention are specificallyillustrated and described herein. However, it will be appreciated thatmodifications and variations of the present invention are encompassed bythe above teachings and within the purview of the appended claimswithout departing from the spirit and intended scope of the invention.

EXAMPLE 1 Process for Extraction, Isolation and Identification ofReplikins and the Use of Replikins to Target, Label or DestroyReplikin-Containing Organisms

[0511] a) Algae

[0512] The following algae were collected from Bermuda water sites andeither extracted on the same day or frozen at −20 degrees C. andextracted the next day. The algae were homogenized in a cold room (at 0to 5 degrees C.) in 1 gram aliquots in neutral buffer, for example 100cc. of 0.005M phosphate buffer solution, pH 7 (“phosphate buffer”) for15 minutes in a Waring blender, centrifuged at 3000 rpm, and thesupernatant concentrated by perevaporation and dialyzed againstphosphate buffer in the cold to produce a volume of approximately 15 ml.The volume of this extract solution was noted and an aliquot taken forprotein analysis, and the remainder was fractionated to obtain theprotein fraction having a pK range between 1 and 4.

[0513] The preferred method of fractionation is chromatography asfollows: The extract solution is fractionated in the cold room (4degrees C.) on a DEAE cellulose (Cellex-D) column 2.5×11.0 cm, which hasbeen equilibrated with 0.005M phosphate buffer. Stepwise eluting solventchanges are made with the following solutions:

[0514] Solution 1—4.04 g. NaH2PO4 and 0.5 g NaH2PO4 are dissolved in 15litres of distilled water (0.005 molar, pH 7);

[0515] Solution 2—8.57 g. NaH2PO4 is dissolved in 2,480 ml. of distilledwater;

[0516] Solution 3—17.1 g. of NaH2PO4 is dissolved in 2480 ml ofdistilled water (0.05 molar, pH 4.7);

[0517] Solution 4—59.65 g. of NaH2PO4 is dissolved in 2470 ml distilledwater (0.175 molar);

[0518] Solution 5—101.6 g. of NaH2PO₄ is dissolved in 2455 ml distilledwater (pH 4.3);

[0519] Solution 6—340.2 g. of NaH2PO4 is dissolved in 2465 of distilledwater (1.0 molar, pX-i 4.1);

[0520] Solution 7—283.63 g. of 80% phosphoric acid (H3PO₄) is made up in2460 ml of distilled water (1.0 molar, pH 1.0).

[0521] The extract solution, in 6 to 10 ml volume, is passed onto thecolumn and overlayed with Solution 1, and a reservoir of 300 ml ofSolution 1 is attached and allowed to drip by gravity onto the column.Three ml aliquots of eluant are collected and analyzed for proteincontent at OD 280 until all of the protein to be removed with Solution 1has been removed from the column. Solution 2 is then applied to thecolumn, followed in succession by Solutions 3, 4, 5, 6 and 7 until allof the protein which can, be removed with each Solution is removed fromthe column. The eluates from Solution 7 are combined, dialyzed againstphosphate buffer, the protein content determined of both dialysand anddialyzate, and both analyzed by gel electrophoresis. One or two bands ofpeptide or protein of molecular weight between 3,000 and 25,000 Daltonsare obtained in Solution 7. For example the algae Caulerpa mexicana,Laurencia obtura, Cladophexa prolifera, Sargassum natans, Caulerpaverticillata, Halimeda tuna, and Penicillos capitatus, after extractionand treatment as above, all demonstrated in Solution 7 eluates sharppeptide bands in this molecular weight region with no contaminants.These Solution 7 proteins or their eluted bands are hydrolyzed, and theamino acid composition determined. The peptides so obtained, which havea lysine composition of 6% or greater are Replikin precursors. TheseReplikin peptide precursors are then determined for amino acid sequenceand the Replikins are determined by hydrolysis and mass spectrometry asdetailed in U.S. Pat. No. 6,242,578 B1. Those which fulfill the criteriadefined by the “3-point-recognition” method are identified as Replikins.This procedure can also be applied to obtain yeast, bacterial and anyplant Replikins.

[0522] b) Virus

[0523] Using the same extraction and column chromatography separationmethods as above in a) for algae, Replikens in virus-infected cells areisolated and identified.

[0524] c) Tumor Cells in vivo and in vitro Tissue Culture

[0525] Using the same extraction and column chromatography separationmethods as above in a) for algae, Replikins in tumor cells are isolatedand identified. For example, Replikin precursors of Astrocytin isolatedfrom malignant brain tumors, Malignin (Aglyco lOB) isolated fromglioblastoma tumor cells in tissue culture, MCF7 mammary carcinoma cellsin tissue culture, and P3J Lymphoma cells in tissue culture each treatedas above in a) yielded Replikin precursors with lysine content of 9.1%,6.7%, 6.7%, and 6.5% respectively. Hydrolysis and mass spectrometry ofAglyco lOB as described in Example 10 U.S. Pat. No. 6,242,578 B1produced the amino acid sequence, ykagvaflhkkndiide the 16-mer Replikin.

EXAMPLE 2

[0526] As an example of diagnostic use of Replikins: Aglyco lOB or the16-mer Repliken may be used as antigen to capture and quantify theamount of its corresponding antibody present in serum for diagnosticpurposes are as shown in FIGS. 2, 3, 4 and 7 of U.S. Pat. No. 6,242,578B1.

[0527] As an example of the production of agents to attach to Replikinsfor labeling, nutritional or destructive purposes: Injection of the16-mer Replikin into rabbits to produce the specific antibody to the16-mer Replikin is shown in Example 6 and FIGS. 9A and 9B of U.S. Pat.No. 6,242,578 B1.

[0528] As an example of the use of agents to label Replikins: The use ofantibodies to the 16-mer Replikin to label specific cells which containthis Replikin is shown in FIG. 5 and Example 6 of U.S. Pat. No.6,242,578 B1.

[0529] As an example of the use of agents to destroy Replikins: The useof antibodies to the 16-mer Replikin to inhibit or destroy specificcells which contain this Replikin is shown in FIG. 6 of U.S. Pat. No.6,242,578 B1.

EXAMPLE 3

[0530] Analysis of sequence data of isolates of influenza virushemagglutinin protein or neuramimidase protein for the presence andconcentration of Replikins is carried out by visual scanning ofsequences or through use of a computer program based on the 3-pointrecognition system described herein. Isolates of influenza virus areobtained and the amino acid sequence of the influenza hemagglutininand/or neuramimidase protein is obtained by any art known method, suchas by sequencing the hemagglutinin or neuramimidase gene and derivingthe protein sequence therefrom. Sequences are scanned for the presenceof new Replikins, conservation of Replikins over time and concentrationof Replikins in each isolate. Comparison of the Replikin sequences andconcentrations to the amino acid sequences obtained from isolates at anearlier time, such as about six months to about three years earlier,provides data that are used to predict the emergence of strains that aremost likely to be the cause of influenza in upcoming flu seasons, andthat form the basis for seasonal influenza peptide vaccines or nucleicacid based vaccines. Observation of an increase in concentration,particularly a stepwise increase in concentration of Replikins in agiven strain of influenza virus for a period of about six months toabout three years or more is a predictor of emergence of the strain as alikely cause of influenza epidemic or pandemic in the future.

[0531] Peptide vaccines or nucleic acid-based vaccines based on theReplikins observed in the emerging strain are generated. An emergingstrain is identified as the strain of influenza virus having the highestincrease in concentration of Replikin sequences within the hemagglutininand/or neuramimidase sequence during the time period. Preferably, thepeptide or nucleic acid vaccine is based on or includes any Replikinsequences that are observed to be conserved in the emerging strain.Conserved Replikins are preferably those Replikin sequences which arepresent in the hemagglutinin or neuramimidase protein sequence for abouttwo years and preferably longer. The vaccines may include anycombination of Replikin sequences identified in the emerging strain.

[0532] For vaccine production, the Replikin peptide or peptidesidentified as useful for an effective vaccine are synthesized by anymethod, including chemical synthesis and molecular biology techniques,including cloning, expression in a host cell and purification therefrom.The peptides are preferably admixed with a pharmaceutically acceptablecarrier in an amount determined to induce a therapeutic antibodyreaction thereto. Generally, the dosage is about 0.1 μg to about 10 mg.

[0533] The influenza vaccine is preferably administered to a patient inneed thereof prior to the onset of “flu season.” Influenza flu seasongenerally occurs in late October and lasts through late April. However,the vaccine may be administered at any time during the year. Preferably,the influenza vaccine is administered once yearly, and is based onReplikin sequences observed to be present, and preferably conserved inthe emerging strain of influenza virus. Another preferred Replikin forinclusion in an influenza vaccine is a Replikin demonstrated to havere-emerged in a strain of influenza after an absence of one or moreyears.

EXAMPLE 4

[0534] Analysis of sequence data of isolates of Plasmodium falciparumantigens for the presence and concentration of Replikins is carried outby visual scanning of sequences or through use of a computer programbased on the 3-point recognition method described herein. Isolates ofPlasmodium falciparum are obtained and the amino acid sequence of theprotein is obtained by any art known method, such as by sequencing thegene and deriving the protein sequence therefrom. Sequences are scannedfor the presence of Replikins, conservation of Replikins over time andconcentration of Replikins in each isolate. This information providesdata that are used to form the basis for anti-malarial peptide vaccinesor nucleic acid based vaccines.

[0535] Peptide vaccines or nucleic acid-based vaccines based on theReplikins observed in the malaria causing organism are generated.Preferably, the peptide or nucleic acid vaccine is based on or includesany Replikin sequences that are observed to be present on a surfaceantigen of the organism. The vaccines may include any combination ofReplikin sequences identified in the malaria causing strain.

[0536] For vaccine production, the Replikin peptide or peptidesidentified as useful for an effective vaccine are synthesized by anymethod, including chemical synthesis and molecular biology techniques,including cloning, expression in a host cell and purification therefrom.The peptides are preferably admixed with a pharmaceutically acceptablecarrier in an amount determined to induce a therapeutic antibodyreaction thereto. Generally, the dosage is about 0.1 μg to about 10 mg.

[0537] Then malaria vaccine is preferably administered to a patient inneed thereof at any time during the year, and particularly prior totravel to a tropical environment.

[0538] Another embodiment includes an antisense nucleic acid moleculecomplementary to the coding strand of the gene or the mRNA encodingorganism for the replikins in organisms including, but not limited to,viruses, trypanosomes, bacteria, fungi, algae, amoeba, and plants,wherein said antisense nucleic acid molecules is complementary to anucleotide sequence of a replikin containing organism.

1 729 1 10 PRT Artificial Sequence Description of Artificial SequenceSynthetic glioma replikin 1 Lys Ala Gly Val Ala Phe Leu His Lys Lys 1 510 2 13 PRT Saccharomyces cerevisiae 2 His Ser Ile Lys Arg Glu Leu GlyIle Ile Phe Asp Lys 1 5 10 3 10 PRT Gemini vinis virus 3 His Lys Gln LysIle Val Ala Pro Val Lys 1 5 10 4 16 PRT Unknown Organism Description ofUnknown Organism Virus recognin 4 Tyr Lys Ala Gly Val Ala Phe Leu HisLys Lys Asn Asp Ile Asp Glu 1 5 10 15 5 10 PRT Human immunodeficiencyvirus type 1 5 Lys Cys Phe Asn Cys Gly Lys Glu Gly His 1 5 10 6 11 PRTHuman immunodeficiency virus type 1 6 Lys Val Tyr Leu Ala Trp Val ProAla His Lys 1 5 10 7 10 PRT Human immunodeficiency virus type 2 7 LysCys Trp Asn Cys Gly Lys Glu Gly His 1 5 10 8 11 PRT Maize streak virus 8Lys Tyr Ile Val Cys Ala Arg Glu Ala His Lys 1 5 10 9 17 PRT Maize streakvirus 9 Lys Glu Lys Lys Pro Ser Lys Asp Glu Ile Met Arg Asp Ile Ile Ser1 5 10 15 His 10 9 PRT Staphylococcus aureus 10 Lys Lys Glu Lys Thr ThrHis Asn Lys 1 5 11 10 PRT Bovine herpesvirus 4 11 His Lys Ile Asn IleThr Asn Gly Gln Lys 1 5 10 12 10 PRT Meleagrid herpesvirus 1 12 His LysAsp Leu Tyr Arg Leu Leu Met Lys 1 5 10 13 15 PRT Unknown OrgansimDescription of Unknown Organism Virus recognin 13 Lys Phe Arg Ile AsnAla Lys Asn Tyr Phe Leu Thr Tyr Pro His 1 5 10 15 14 19 PRT UnknownOrganism Description of Unknown Organism Virus recognin 14 Lys Asn LeuGlu Thr Pro Val Asn Lys Leu Phe Ile Arg Ile Cys Arg 1 5 10 15 Glu PheHis 15 14 PRT Unknown Organism Description of Unknown Organism Virusrecognin 15 His Pro Asn Ile Gln Ala Ala Lys Ser Ser Thr Asp Val Lys 1 510 16 19 PRT Unknown Organism Description of Unknown Organism Virusrecognin 16 Lys Ser Ser Thr Asp Val Lys Ala Tyr Met Asp Lys Asp Gly AspVal 1 5 10 15 Leu Asp His 17 21 PRT Unknown Organism Description ofUnknown Organism Virus recognin 17 Lys Ala Ser Ala Leu Asn Ile Leu ArgGlu Lys Ala Pro Lys Asp Phe 1 5 10 15 Val Leu Gln Phe His 20 18 13 PRTHepatitis C virus 18 His Tyr Pro Pro Lys Pro Gly Cys Ile Val Pro Ala Lys1 5 10 19 4 PRT Homo sapiens 19 Tyr Lys Ala Gly 1 20 6 PRT Homo sapiens20 Tyr Lys Ala Gly Val Ala 1 5 21 7 PRT Homo sapiens 21 Tyr Lys Ala GlyVal Ala Phe 1 5 22 7 PRT Homo sapiens 22 Tyr Lys Ala Gly Val Ala Phe 1 523 9 PRT Homo sapiens 23 Ala Gly Val Ala Phe His Lys Lys Asn 1 5 24 4PRT Homo sapiens 24 Gly Val Ala Phe 1 25 3 PRT Homo sapiens 25 Val AlaPhe 1 26 7 PRT Homo sapiens 26 Val Ala Phe Leu His Lys Lys 1 5 27 7 PRTHomo sapiens 27 Val Ala Phe Leu His Lys Lys 1 5 28 9 PRT Homo sapiens 28Val Ala Phe Leu His Lys Lys Asn Asp 1 5 29 8 PRT Homo sapiens 29 Val AlaPhe His Lys Lys Asn Asp 1 5 30 4 PRT Homo sapiens 30 Ala Phe Leu His 131 8 PRT Homo sapiens 31 His Lys Lys Asn Asp Ile Asp Glu 1 5 32 6 PRTHomo sapiens 32 Lys Lys Asn Asp Ile Asp 1 5 33 6 PRT Homo sapiens 33 LysAsn Asp Ile Asp Glu 1 5 34 8 PRT Caldophera prolifera 34 Lys Ala Ser LysPhe Thr Lys His 1 5 35 12 PRT Isolepis prolifera 35 Lys Ala Gln Ala GluThr Gly Glu Ile Lys Gly His 1 5 10 36 10 PRT Schizosaccharomyces pombe36 Lys Ser Phe Lys Tyr Pro Lys Lys His Lys 1 5 10 37 10 PRT Oryza sativa37 Lys Lys Ala Tyr Gly Asn Glu Leu His Lys 1 5 10 38 9 PRT Penicilliummarneffei 38 Lys Val Asp Ile Val Thr His Gln Lys 1 5 39 12 PRT Diseuladcstructiva 39 Lys Leu Glu Glu Asp Ala Ala Tyr His Arg Lys Lys 1 5 10 4017 PRT Ophiostoma novo-ulmi 40 Lys Val Ile Leu Pro Leu Arg Gly Asn IleLys Gly Ile Phe Phe Lys 1 5 10 15 His 41 11 PRT Entamoeba invadens 41Lys Leu Ile Leu Lys Gly Asp Leu Asn Lys His 1 5 10 42 8 PRT Helicobacterpylori 42 Lys Ser Val His Ala Phe Leu Lys 1 5 43 9 PRT Mycoplasmapulmonis 43 Lys Val His Phe Phe Gln Leu Lys Lys 1 5 44 9 PRT Arabidopsisthaliana 44 Lys Asp His Asp Phe Asp Gly Asp Lys 1 5 45 11 PRTArabidopsis thaliana 45 Lys Met Lys Gly Leu Lys Gln Lys Lys Ala His 1 510 46 12 PRT Arabidopsis thaliana 46 Lys Glu Leu Ser Ser Thr Thr Gln GluLys Ser His 1 5 10 47 9 PRT Feline immunodeficiency virus 47 His Leu LysAsp Tyr Lys Leu Val Lys 1 5 48 7 PRT Rous sarcoma virus 48 Lys Lys LeuArg His Glu Lys 1 5 49 7 PRT Avian sarcoma virus 49 Lys Lys Leu Arg HisAsp Lys 1 5 50 7 PRT Homo sapiens 50 Lys Lys Leu Arg His Asp Lys 1 5 517 PRT Avian sarcoma virus 51 Lys Lys Leu Arg His Glu Lys 1 5 52 7 PRTHomo sapiens 52 Lys Lys Leu Arg His Glu Lys 1 5 53 8 PRT Homo sapiens 53Lys Gln Ala His Glu Leu Ala Lys 1 5 54 8 PRT Polyama virus 54 Lys ThrHis Arg Phe Ser Lys His 1 5 55 8 PRT Sindbis virus 55 Lys Asn Leu HisGlu Lys Ile Lys 1 5 56 9 PRT Human papilloamavirus type 71 56 Lys HisArg Pro Leu Leu Gln Leu Lys 1 5 57 7 PRT Avian encephalomyelitis virus57 Lys Ser Pro Asn His Val Lys 1 5 58 8 PRT Feline sarcoma virus 58 LysAsn Ile His Leu Glu Lys Lys 1 5 59 8 PRT Homo sapiens 59 Lys Asn Ile HisLeu Glu Lys Lys 1 5 60 10 PRT Polyoma virus 60 Lys Pro His Leu Ala GlnSer Leu Glu Lys 1 5 10 61 9 PRT Polyoma virus 61 Lys Gln His Arg Glu LeuLys Asp Lys 1 5 62 9 PRT Polyoma virus 62 Lys Gln His Arg Glu Leu LysAsp Lys 1 5 63 12 PRT Murine leukemia virus 63 Lys Val Pro Val Leu IleSer Pro Thr Leu Lys His 1 5 10 64 13 PRT Human T-cell lymphotropic virustype 2 64 Lys Ser Leu Leu Leu Glu Val Asp Lys Asp Ile Ser His 1 5 10 6513 PRT Homo sapiens 65 Lys Ala Gly Ile Thr Ile Met Val Lys Arg Glu TyrHis 1 5 10 66 8 PRT Homo sapiens 66 Lys Ser Gly Lys His Leu Gly Lys 1 567 9 PRT Homo sapiens 67 Lys Arg Arg Glu Gln Leu Lys His Lys 1 5 68 10PRT Homo sapiens 68 Lys Ser Phe Glu Val Ile Lys Val Ile His 1 5 10 69 8PRT Homo sapiens 69 Lys Lys Lys His Thr Val Lys Lys 1 5 70 9 PRT Homosapiens 70 Lys Ala Gln Lys Asp His Leu Ser Lys 1 5 71 10 PRT Homosapiens 71 His Leu Lys Arg Val Lys Asp Leu Lys Lys 1 5 10 72 11 PRT Homosapiens 72 Lys Tyr Gly Ser Pro Lys His Arg Leu Ile Lys 1 5 10 73 13 PRTPapilloma virus type 11 73 Lys Leu Lys His Ile Leu Gly Lys Ala Arg PheIle Lys 1 5 10 74 12 PRT Homo sapiens 74 Lys Gly Asp His Val Lys His TyrLys Ile Arg Lys 1 5 10 75 13 PRT Homo sapiens 75 Lys Glu Lys Leu Arg AspVal Met Val Asp Arg His Lys 1 5 10 76 15 PRT Homo sapiens 76 Lys Leu GlnAla Arg Gln Gln Gln Leu Leu Lys Lys Ile Glu His 1 5 10 15 77 14 PRT Homosapiens 77 Lys Lys Gly Asn Arg Val Ser Pro Thr Met Lys Val Thr His 1 510 78 9 PRT Homo sapiens 78 Lys Glu Ile Pro Leu His Phe Arg Lys 1 5 79 8PRT Homo sapiens 79 Lys Lys Lys Pro His Ile Lys Lys 1 5 80 9 PRT Homosapiens 80 Lys Thr Arg His Asp Pro Leu Ala Lys 1 5 81 10 PRT Homosapiens 81 Lys His His Pro Lys Asp Asn Leu Ile Lys 1 5 10 82 10 PRT Homosapiens 82 Lys His Lys Arg Lys Lys Phe Arg Gln Lys 1 5 10 83 10 PRT Homosapiens 83 Lys Ala Gly Val Ala Phe Leu His Lys Lys 1 5 10 84 10 PRT Homosapiens 84 Lys His Lys Arg Lys Lys Phe Arg Gln Lys 1 5 10 85 10 PRT Homosapiens 85 Lys Lys Lys Ser Lys Lys His Lys Asp Lys 1 5 10 86 11 PRT Homosapiens 86 His Lys Ser Glu Lys Pro Ala Leu Pro Arg Lys 1 5 10 87 14 PRTHomo sapiens 87 Lys Lys Lys Lys Pro Ser Arg Leu Lys Gly Asp Asn Glu Lys1 5 10 88 16 PRT Homo sapiens 88 Lys Thr Lys Lys Gly Asn Arg Val Ser ProThr Met Lys Val Thr His 1 5 10 15 89 18 PRT Homo sapiens 89 Lys His LysGlu Lys Met Ser Lys Asp Gly Lys Lys Lys Lys Lys Lys 1 5 10 15 Ser Lys 909 PRT Legionella sp. 90 Lys Ile His Leu Ile Ser Val Lys Lys 1 5 91 8 PRTInfluenza B virus 91 Lys Ser His Phe Ala Asn Leu Lys 1 5 92 11 PRTInfluenza B virus 92 Lys Ser His Phe Ala Asn Leu Lys Gly Thr Lys 1 5 1093 19 PRT Influenza B virus 93 Lys Ser His Phe Ala Asn Leu Lys Gly ThrLys Thr Arg Gly Lys Leu 1 5 10 15 Cys Pro Lys 94 9 PRT Influenza B virus94 His Glu Lys Tyr Gly Gly Leu Asn Lys 1 5 95 11 PRT Influenza B virus95 His Glu Lys Tyr Gly Gly Leu Asn Lys Ser Lys 1 5 10 96 20 PRTInfluenza B virus 96 His Glu Lys Tyr Gly Gly Leu Asn Lys Ser Lys Pro TyrTyr Thr Gly 1 5 10 15 Glu His Ala Lys 20 97 13 PRT Influenza B virus 97His Ala Lys Ala Ile Gly Asn Cys Pro Ile Trp Val Lys 1 5 10 98 23 PRTInfluenza B virus 98 His Ala Lys Ala Ile Gly Asn Cys Pro Ile Trp Val LysThr Pro Leu 1 5 10 15 Lys Leu Ala Asn Gly Thr Lys 20 99 29 PRT InfluenzaB virus 99 His Ala Lys Ala Ile Gly Asn Cys Pro Ile Trp Val Lys Thr ProLeu 1 5 10 15 Lys Leu Ala Asn Gly Thr Lys Tyr Arg Pro Pro Ala Lys 20 25100 32 PRT Influenza B virus 100 101 13 PRT Influenza B virus 101 HisPhe Ala Asn Leu Lys Gly Thr Lys Thr Arg Gly Lys 1 5 10 102 17 PRTInfluenza B virus 102 103 16 PRT Influenza B virus 103 His Ser Asp AsnGlu Ile Gln Met Val Lys Leu Tyr Gly Asp Ser Lys 1 5 10 15 104 21 PRTInfluenza B virus 104 His Ser Asp Asn Glu Ile Gln Asp Lys Met Val LysLeu Tyr Gly Asp 1 5 10 15 Ser Lys Pro Gln Lys 20 105 19 PRT Influenza Bvirus 105 106 9 PRT Influenza B virus MOD_RES (2) ala or val 106 Lys XaaSer Ile Leu His Glu Val Lys 1 5 107 15 PRT Influenza B virus 107 Lys CysThr Gly Thr Ile Pro Ser Ala Lys Ala Ser Ile Leu His 1 5 10 15 108 18 PRTInfluenza B virus 108 Lys Cys Thr Gly Thr Ile Pro Ser Ala Lys Ala SerIle Leu His Glu 1 5 10 15 Val Lys 109 16 PRT Influenza B virus 109 LysTyr Gly Gly Leu Asn Lys Ser Lys Pro Tyr Tyr Thr Gly Glu His 1 5 10 15110 26 PRT Influenza B virus 110 Lys Val Trp Cys Ala Ser Gly Arg Ser LysVal Ile Lys Gly Ser Leu 1 5 10 15 Pro Leu Ile Gly Glu Ala Asp Cys LeuHis 20 25 111 10 PRT Influenza B virus 111 Lys Pro Tyr Tyr Thr Gly GluHis Ala Lys 1 5 10 112 18 PRT Influenza B virus 112 Lys Cys Met Gly ThrIle Pro Ser Ala Lys Ala Ser Ile Leu His Glu 1 5 10 15 Val Lys 113 15 PRTInfluenza B virus 113 His Asn Val Ile Asn Ala Glu Lys Ala Pro Gly GlyPro Tyr Lys 1 5 10 15 114 16 PRT Influenza B virus 114 His Ser Asp AsnGlu Thr Gln Met Ala Lys Leu Tyr Gly Asp Ser Lys 1 5 10 15 115 18 PRTInfluenza B virus 115 His Gly Val Ala Val Ala Ala Asp Leu Lys Ser ThrGln Glu Ala Ile 1 5 10 15 Asn Lys 116 29 PRT Influenza B virus 116 HisGly Val Ala Val Ala Ala Asp Leu Lys Ser Thr Gln Glu Ala Ile 1 5 10 15Asn Lys Asp Thr Ile Ser Thr Gln Glu Ala Ile Asn Lys 20 25 117 21 PRTInfluenza B virus 117 Lys Leu Tyr Gly Asp Ser Lys Pro Gln Lys Phe ThrSer Ser Ala Asn 1 5 10 15 Gly Val Thr Thr His 20 118 19 PRT Influenza Bvirus 118 His Ser Asp Asn Glu Thr Gln Met Ala Lys Leu Tyr Gly Asp SerLys 1 5 10 15 Pro Gln Lys 119 13 PRT Influenza B virus 119 His Phe AlaAsn Leu Lys Gly Thr Gln Thr Arg Gly Lys 1 5 10 120 12 PRT Influenza Bvirus 120 Lys Pro Arg Ser Ala Leu Lys Cys Lys Gly Phe His 1 5 10 121 22PRT Influenza B virus MOD_RES (15) gly or ala 121 Lys Ser Lys Pro TyrTyr Thr Gly Glu His Ala Lys Ala Ile Xaa Asn 1 5 10 15 Cys Pro Ile TrpVal Lys 20 122 16 PRT Influenza virus MOD_RES (3) val or ile 122 His ProXaa Thr Ile Gly Glu Cys Pro Lys Tyr Val Xaa Xaa Xaa Lys 1 5 10 15 123 21PRT Influenza virus MOD_RES (10) glu or gly 123 His Asp Ser Asn Val LysAsn Leu Tyr Xaa Lys Val Xaa Xaa Gln Leu 1 5 10 15 Xaa Asn Asn Ala Lys 20124 17 PRT Influenza virus MOD_RES (10) glu or gly 124 His Asp Ser AsnVal Lys Asn Leu Tyr Xaa Lys Val Xaa Xaa Gln Leu 1 5 10 15 Lys 125 36 PRTInfluenza virus MOD_RES (4)..(5) asn or asp 125 His Lys Cys Xaa Xaa XaaCys Met Glu Ser Val Xaa Asn Gly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys TyrSer Glu Glu Ser Lys Leu Asn Arg Glu Xaa Ile 20 25 30 Asp Gly Val Lys 35126 26 PRT Influenza virus MOD_RES (4)..(5) asn or asp 126 His Lys CysXaa Xaa Xaa Cys Met Glu Ser Val Xaa Asn Gly Thr Tyr 1 5 10 15 Asp TyrPro Lys Tyr Ser Glu Glu Ser Lys 20 25 127 50 PRT Influenza virus MOD_RES(4) glu or gly 127 His Gln Asn Xaa Gln Gly Ser Gly Tyr Ala Ala Asp GlnLys Ser Thr 1 5 10 15 Gln Asn Ala Ile Xaa Gly Ile Thr Asn Lys Val AsnSer Val Ile Glu 20 25 30 Lys Met Asn Thr Gln Phe Thr Ala Val Gly Lys GluPhe Asn Lys Leu 35 40 45 Glu Lys 50 128 33 PRT Influenza virus MOD_RES(4) glu or gly 128 His Gln Asn Xaa Gln Gly Ser Gly Tyr Ala Ala Asp GlnLys Ser Thr 1 5 10 15 Gln Asn Ala Ile Xaa Gly Ile Thr Asn Lys Val AsnSer Val Ile Glu 20 25 30 Lys 129 26 PRT Influenza virus MOD_RES (4) gluor gly 129 His Gln Asn Xaa Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys SerThr 1 5 10 15 Gln Asn Ala Ile Xaa Gly Ile Thr Asn Lys 20 25 130 14 PRTInfluenza virus 130 Lys Phe Glu Ile Phe Pro Lys Thr Ser Ser Trp Pro AsnHis 1 5 10 131 27 PRT Influenza virus MOD_RES (3) asn, ser or thr 131Lys Gly Xaa Ser Tyr Pro Lys Leu Xaa Lys Ser Tyr Xaa Asn Asn Lys 1 5 1015 Gly Lys Glu Val Leu Val Leu Trp Gly Val His 20 25 132 18 PRTInfluenza virus MOD_RES (4) val or thr 132 Lys Ser Tyr Xaa Asn Asn LysGly Lys Glu Val Leu Val Leu Trp Gly 1 5 10 15 Val His 133 36 PRTInfluenza virus 133 His Lys Cys Asn Asn Glu Cys Met Glu Ser Val Lys AsnGly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu AsnArg Glu Lys Ile 20 25 30 Asp Gly Val Lys 35 134 26 PRT Influenza virus134 His Lys Cys Asn Asn Glu Cys Met Glu Ser Val Lys Asn Gly Thr Tyr 1 510 15 Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys 20 25 135 20 PRT Influenzavirus 135 His Lys Cys Asn Asn Glu Cys Met Glu Ser Val Lys Asn Gly ThrTyr 1 5 10 15 Asp Tyr Pro Lys 20 136 12 PRT Influenza virus 136 His LysCys Asn Asn Glu Cys Met Glu Ser Val Lys 1 5 10 137 34 PRT Influenzavirus MOD_RES (9) lys or arg 137 His Asn Gly Lys Ser Ser Phe Tyr Xaa AsnLeu Leu Trp Leu Thr Xaa 1 5 10 15 Lys Asn Gly Leu Tyr Pro Asn Leu SerLys Ser Tyr Val Asn Asn Lys 20 25 30 Glu Lys 138 32 PRT Influenza virusMOD_RES (9) lys or arg 138 His Asn Gly Lys Ser Ser Phe Tyr Xaa Asn LeuLeu Trp Leu Thr Xaa 1 5 10 15 Lys Asn Gly Leu Tyr Pro Asn Leu Ser LysSer Tyr Val Asn Asn Lys 20 25 30 139 26 PRT Influenza virus MOD_RES (9)lys or arg 139 His Asn Gly Lys Ser Ser Phe Tyr Xaa Asn Leu Leu Trp LeuThr Xaa 1 5 10 15 Lys Asn Gly Leu Tyr Pro Asn Leu Ser Lys 20 25 140 17PRT Influenza virus MOD_RES (9) lys or arg 140 His Asn Gly Lys Ser SerPhe Tyr Xaa Asn Leu Leu Trp Leu Thr Xaa 1 5 10 15 Lys 141 40 PRTInfluenza virus 141 Lys Ser Ser Phe Tyr Lys Asn Leu Leu Trp Leu Thr GluLys Asn Gly 1 5 10 15 Leu Tyr Pro Asn Leu Ser Lys Ser Tyr Val Asn AsnLys Glu Lys Glu 20 25 30 Val Leu Val Leu Trp Gly Val His 35 40 142 35PRT Influenza virus 142 Lys Asn Leu Leu Trp Leu Thr Glu Lys Asn Gly LeuTyr Pro Asn Leu 1 5 10 15 Ser Lys Ser Tyr Val Asn Asn Lys Glu Lys GluVal Leu Val Leu Trp 20 25 30 Gly Val His 35 143 27 PRT Influenza virus143 Lys Asn Gly Leu Tyr Pro Asn Leu Ser Lys Ser Tyr Val Asn Asn Lys 1 510 15 Glu Lys Glu Val Leu Val Leu Trp Gly Val His 20 25 144 18 PRTInfluenza virus MOD_RES (4) val or ala 144 Lys Ser Tyr Xaa Asn Asn LysGlu Lys Glu Val Xaa Xaa Leu Trp Gly 1 5 10 15 Val His 145 12 PRTInfluenza virus 145 Lys Glu Ser Ser Trp Pro Asn His Thr Val Thr Lys 1 510 146 44 PRT Influenza virus MOD_RES (4) thr or asn 146 His Glu Thr XaaLys Gly Val Thr Ala Ala Cys Pro Tyr Ala Gly Ala 1 5 10 15 Ser Ser PheTyr Arg Asn Leu Leu Trp Leu Val Lys Lys Glu Asn Ser 20 25 30 Tyr Pro LysLeu Ser Lys Ser Tyr Val Asn Asn Lys 35 40 147 38 PRT Influenza virusMOD_RES (4) thr or asn 147 His Glu Thr Xaa Lys Gly Val Thr Ala Ala CysPro Tyr Ala Gly Ala 1 5 10 15 Ser Ser Phe Tyr Arg Asn Leu Leu Trp LeuVal Lys Lys Glu Asn Ser 20 25 30 Tyr Pro Lys Leu Ser Lys 35 148 22 PRTInfluenza virus 148 Lys Phe Glu Ile Phe Pro Lys Thr Ser Ser Trp Pro AsnGlu Val Leu 1 5 10 15 Val Leu Trp Gly Val His 20 149 8 PRT Influenzavirus 149 Lys Glu Arg Ser Trp Pro Lys His 1 5 150 21 PRT Influenza virus150 Lys Leu Ser Lys Ser Tyr Val Asn Asn Lys Glu Lys Glu Val Leu Val 1 510 15 Leu Trp Gln Val His 20 151 15 PRT Influenza virus 151 Lys Asn AsnLys Glu Lys Glu Val Leu Val Leu Trp Gln Val His 1 5 10 15 152 34 PRTInfluenza virus MOD_RES (2) lys or asn 152 His Xaa Xaa Lys Ser Ser PheTyr Xaa Asn Leu Leu Trp Leu Thr Glu 1 5 10 15 Lys Asn Gly Xaa Tyr ProXaa Leu Ser Lys Ser Tyr Ala Asn Asn Lys 20 25 30 Glu Lys 153 17 PRTInfluenza virus MOD_RES (2) lys or asn 153 His Xaa Xaa Lys Ser Ser PheTyr Xaa Asn Leu Leu Trp Leu Thr Glu 1 5 10 15 Lys 154 9 PRT Influenzavirus 154 His Ala Lys Lys Ser Ser Phe Tyr Lys 1 5 155 11 PRT Influenzavirus 155 His Asn Gly Lys Leu Cys Arg Leu Lys Gly Lys 1 5 10 156 9 PRTInfluenza virus MOD_RES (7) gln or gly 156 His Tyr Lys Leu Asn Asn XaaLys Lys 1 5 157 25 PRT Influenza virus 157 His Asp Ile Tyr Arg Asp GluAla Ile Asn Asn Arg Phe Gln Ile Gln 1 5 10 15 Gly Val Lys Leu Thr GlnGly Tyr Lys 20 25 158 11 PRT Influenza virus 158 Lys Gly Asn Gly Cys PheGlu Ile Phe His Lys 1 5 10 159 18 PRT Influenza virus 159 Lys Leu AsnArg Leu Ile Glu Lys Thr Asn Asp Lys Tyr His Gln Ile 1 5 10 15 Glu Lys160 14 PRT Influenza virus 160 Lys Leu Asn Arg Leu Ile Glu Lys Thr AsnAsp Lys Tyr His 1 5 10 161 13 PRT Influenza virus 161 Lys Cys His ThrAsp Lys Gly Ser Leu Ser Thr Thr Lys 1 5 10 162 16 PRT Influenza virus162 Lys Ile Asn Asn Gly Asp Tyr Ala Lys Leu Tyr Ile Trp Gly Val His 1 510 15 163 17 PRT Influenza virus 163 His Asn Gly Lys Leu Cys Arg Lys GlyIle Ala Pro Leu Gln Leu Gly 1 5 10 15 Lys 164 38 PRT Influenza virus 164His Glu Thr Asn Arg Gln Val Thr Ala Ala Cys Pro Tyr Ala Gly Ala 1 5 1015 Asn Ser Phe Phe Arg Asn Leu Ile Trp Leu Val Lys Lys Glu Ser Ser 20 2530 Tyr Pro Lys Leu Ser Lys 35 165 35 PRT Influenza virus 165 His Glu ThrAsn Arg Gln Val Thr Ala Ala Cys Pro Tyr Ala Gly Ala 1 5 10 15 Asn SerPhe Phe Arg Asn Leu Ile Trp Leu Val Lys Lys Glu Ser Ser 20 25 30 Tyr ProLys 35 166 31 PRT Influenza virus 166 His Pro Pro Thr Ser Thr Asp GlnGln Ser Leu Tyr Gln Asn Ala Asp 1 5 10 15 Ala Tyr Ile Phe Val Gly SerSer Lys Tyr Asn Arg Lys Phe Lys 20 25 30 167 35 PRT Influenza virus 167His Pro Pro Thr Ser Thr Asp Gln Gln Ser Leu Tyr Gln Asn Ala Asp 1 5 1015 Ala Tyr Ile Phe Val Gly Ser Ser Lys Tyr Asn Arg Lys Phe Lys Pro 20 2530 Glu Ile Ala 35 168 25 PRT Influenza virus 168 His Asp Ile Tyr Arg AspGlu Ala Ile Asn Asn Arg Phe Gln Ile Gln 1 5 10 15 Gly Val Lys Ile ThrGln Gly Tyr Lys 20 25 169 43 PRT Influenza virus 169 His Gln Asn Glu GlnGly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr 1 5 10 15 Gln Asn Ala IleAsp Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu 20 25 30 Lys Met Asn ThrGln Phe Thr Ala Val Gly Lys 35 40 170 33 PRT Influenza virus 170 His GlnAsn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr 1 5 10 15 GlnAsn Ala Ile Asp Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu 20 25 30 Lys171 50 PRT Influenza virus 171 His Gln Asn Glu Gln Gly Ser Gly Tyr AlaAla Asp Gln Lys Ser Thr 1 5 10 15 Gln Asn Ala Ile Asn Gly Ile Thr AsnLys Val Asn Ser Val Ile Glu 20 25 30 Lys Met Asn Thr Gln Phe Thr Ala ValGly Lys Glu Phe Asn Lys Leu 35 40 45 Glu Lys 50 172 18 PRT Influenzavirus 172 His Asn Gly Lys Leu Cys Arg Leu Lys Gly Ile Ala Pro Leu GlnLeu 1 5 10 15 Gly Lys 173 12 PRT Influenza virus 173 His Lys Cys Asn AsnGlu Cys Met Glu Ser Val Lys 1 5 10 174 14 PRT Influenza virus 174 LysPhe Glu Ile Phe Pro Lys Ala Ser Ser Trp Pro Asn His 1 5 10 175 21 PRTInfluenza virus 175 His Asp Ser Asn Val Lys Asn Leu Tyr Glu Lys Val ArgSer Gln Leu 1 5 10 15 Arg Asn Asn Ala Lys 20 176 22 PRT Influenza virus176 Lys Val Asn Ser Val Ile Lys Lys Met Asn Thr Gln Phe Ala Ala Val 1 510 15 Gly Lys Glu Phe Asn His 20 177 8 PRT Influenza virus 177 Lys HisAsn Gly Lys Leu Cys Lys 1 5 178 28 PRT Influenza virus 178 Lys Lys GlyThr Ser Tyr Pro Lys Leu Ser Lys Ser Tyr Thr His Asn 1 5 10 15 Lys GlyLys Glu Val Leu Val Leu Trp Gly Val His 20 25 179 27 PRT Influenza virus179 Lys Gly Thr Ser Tyr Pro Lys Leu Ser Lys Ser Tyr Thr His Asn Lys 1 510 15 Gly Lys Glu Val Leu Val Leu Trp Gly Val His 20 25 180 21 PRTInfluenza virus 180 Lys Leu Ser Lys Ser Tyr Thr His Asn Lys Gly Lys GluVal Leu Val 1 5 10 15 Leu Trp Gly Val His 20 181 18 PRT Influenza virus181 Lys Ser Tyr Thr His Asn Lys Gly Lys Glu Val Leu Val Leu Trp Gly 1 510 15 Val His 182 10 PRT Influenza virus 182 Lys Gly Val Thr Ala Ser CysSer His Lys 1 5 10 183 34 PRT Influenza virus 183 Lys Gly Val Thr AlaSer Cys Ser His Lys Gly Arg Ser Ser Phe Tyr 1 5 10 15 Arg Asn Leu LeuTrp Leu Thr Glu Lys Asn Gly Leu Tyr Pro Asn Leu 20 25 30 Ser Lys 184 27PRT Influenza virus 184 Lys Gly Asn Ser Tyr Pro Lys Leu Ser Lys Ser TyrVal Asn Asn Lys 1 5 10 15 Glu Lys Glu Val Leu Val Leu Trp Gly Ile His 2025 185 8 PRT Influenza virus 185 Lys Glu Phe Asn His Leu Glu Lys 1 5 18639 PRT Influenza virus 186 His Pro Pro Thr Ser Thr Asp Gln Gln Ser LeuTyr Gln Asn Ala Asp 1 5 10 15 Ala Tyr Val Phe Val Gly Ser Ser Lys TyrAsn Lys Lys Phe Lys Pro 20 25 30 Glu Ile Ala Thr Arg Pro Lys 35 187 31PRT Influenza virus 187 His Pro Pro Thr Ser Thr Asp Gln Gln Ser Leu TyrGln Asn Ala Asp 1 5 10 15 Ala Tyr Val Phe Val Gly Ser Ser Lys Tyr AsnLys Lys Phe Lys 20 25 30 188 31 PRT Influenza virus 188 His Glu Gly LysSer Ser Phe Tyr Arg Asn Leu Leu Trp Leu Thr Glu 1 5 10 15 Lys Glu GlySer Tyr Pro Lys Leu Lys Asn Ser Tyr Val Asn Lys 20 25 30 189 23 PRTInfluenza virus 189 His Glu Gly Lys Ser Ser Phe Tyr Arg Asn Leu Leu TrpLeu Thr Glu 1 5 10 15 Lys Glu Gly Ser Tyr Pro Lys 20 190 26 PRTInfluenza virus 190 His Lys Cys Asp Asn Glu Cys Met Glu Ser Val Arg AsnGly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys 20 25 19112 PRT Influenza virus 191 Lys Glu Ser Ser Trp Pro Asn His Thr Val ThrLys 1 5 10 192 35 PRT Influenza virus 192 Lys Asn Leu Leu Trp Leu ThrGlu Lys Asn Gly Leu Tyr Pro Asn Leu 1 5 10 15 Ser Lys Ser Tyr Val AsnAsn Lys Glu Lys Glu Ile Leu Val Leu Trp 20 25 30 Gly Val His 35 193 27PRT Influenza virus MOD_RES (9) lys or met 193 His Asn Gly Lys Ser SerPhe Tyr Xaa Xaa Leu Leu Trp Leu Thr Xaa 1 5 10 15 Xaa Lys Asn Gly LeuTyr Pro Asn Leu Ser Lys 20 25 194 17 PRT Influenza virus 194 His Asn GlyLys Ser Ser Phe Tyr Lys Asn Leu Leu Trp Leu Thr Glu 1 5 10 15 Lys 195 55PRT Influenza virus 195 His Thr Val Thr Lys Gly Val Thr Ala Ser Cys SerHis Asn Gly Lys 1 5 10 15 Ser Ser Phe Tyr Lys Asn Leu Leu Trp Leu ThrGlu Lys Asn Gly Leu 20 25 30 Tyr Pro Asn Leu Ser Lys Ser Tyr Val Asn AsnLys Glu Lys Glu Val 35 40 45 Leu Val Leu Trp Gly Val His 50 55 196 38PRT Influenza virus MOD_RES (5) lys or gly 196 His Thr Val Thr Xaa GlyVal Xaa Ala Ser Cys Ser His Asn Gly Lys 1 5 10 15 Ser Ser Phe Tyr XaaXaa Leu Leu Trp Leu Thr Xaa Lys Xaa Gly Leu 20 25 30 Tyr Pro Asn Leu SerLys 35 197 29 PRT Influenza virus 197 His Thr Val Thr Lys Gly Val ThrAla Ser Cys Ser His Asn Gly Lys 1 5 10 15 Ser Ser Phe Tyr Lys Asn LeuLeu Trp Leu Thr Glu Lys 20 25 198 48 PRT Influenza virus 198 Lys Tyr ValArg Ser Thr Lys Leu Arg Met Val Thr Gly Leu Arg Asn 1 5 10 15 Ile ProSer Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe 20 25 30 Ile GluGly Gly Trp Thr Gly Met Ile Asp Gly Trp Tyr Gly Tyr His 35 40 45 199 43PRT Influenza virus 199 His Gln Asn Glu Gln Gly Ser Gly Tyr Ala Ala AspGln Lys Ser Thr 1 5 10 15 Gln Asn Ala Ile Asn Gly Ile Thr Asn Lys ValAsn Ser Ile Ile Glu 20 25 30 Lys Met Asn Thr Gln Phe Thr Ala Val Gly Lys35 40 200 33 PRT Influenza virus 200 His Gln Asn Glu Gln Gly Ser Gly TyrAla Ala Asp Gln Lys Ser Thr 1 5 10 15 Gln Asn Ala Ile Asn Gly Ile ThrAsn Lys Val Asn Ser Ile Ile Glu 20 25 30 Lys 201 26 PRT Influenza virus201 His Gln Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Lys Ser Thr 1 510 15 Gln Asn Ala Ile Asn Gly Ile Thr Asn Lys 20 25 202 23 PRT Influenzavirus 202 His Ser Gly Ala Arg Ser Phe Tyr Arg Asn Leu Leu Trp Ile ValLys 1 5 10 15 Lys Gly Asn Ser Tyr Pro Lys 20 203 26 PRT Influenza virus203 His Ser Gly Ala Arg Ser Phe Tyr Arg Asn Leu Leu Trp Ile Val Lys 1 510 15 Lys Gly Asn Ser Tyr Pro Lys Leu Asn Lys 20 25 204 32 PRT Influenzavirus 204 His Ser Gly Ala Arg Ser Phe Tyr Arg Asn Leu Leu Trp Ile ValLys 1 5 10 15 Lys Gly Asn Ser Tyr Pro Lys Leu Asn Lys Ser Tyr Thr AsnAsp Lys 20 25 30 205 34 PRT Influenza virus 205 His Ser Gly Ala Arg SerPhe Tyr Arg Asn Leu Leu Trp Ile Val Lys 1 5 10 15 Lys Gly Asn Ser TyrPro Lys Leu Asn Lys Ser Tyr Thr Asn Asp Lys 20 25 30 Gly Lys 206 16 PRTInfluenza virus 206 His Thr Val Ser Lys Gly Val Thr Thr Ser Cys Ser HisAsn Gly Lys 1 5 10 15 207 12 PRT Influenza virus 207 Lys Ala Thr Ser TrpPro Asn His Glu Thr Thr Lys 1 5 10 208 12 PRT Influenza virus 208 LysGln Val Thr Thr Ser Cys Ser His Asn Gln Lys 1 5 10 209 27 PRT Influenzavirus 209 Lys Gly Asn Ser Tyr Pro Lys Leu Asn Lys Ser Tyr Thr Asn AspLys 1 5 10 15 Gly Lys Glu Val Leu Val Ile Trp Gly Val His 20 25 210 21PRT Influenza virus 210 Lys Leu Asn Lys Ser Tyr Thr Asn Asp Lys Gly LysGlu Val Leu Val 1 5 10 15 Ile Trp Gly Val His 20 211 18 PRT Influenzavirus 211 Lys Ser Tyr Thr Asn Asp Lys Gly Lys Glu Val Leu Val Ile TrpGly 1 5 10 15 Val His 212 35 PRT Influenza virus MOD_RES (16) glu or gln212 His Asn Gln Lys Ser Ser Phe Tyr Arg Asn Leu Leu Trp Leu Thr Xaa 1 510 15 Lys Asn Gly Leu Tyr Pro Asn Leu Ser Lys Ser Tyr Xaa Ala Asn Asn 2025 30 Lys Glu Lys 35 213 16 PRT Influenza virus 213 His Pro Ile Thr IleGly Glu Cys Pro Lys Tyr Val Arg Ser Ala Lys 1 5 10 15 214 43 PRTInfluenza virus 214 His Gln Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp GlnLys Ser Thr 1 5 10 15 Gln Asn Ala Ile Asn Gly Ile Thr Asn Lys Val AsnSer Val Ile Glu 20 25 30 Lys Met Asn Thr Gln Phe Thr Ala Val Gly Lys 3540 215 33 PRT Influenza virus 215 His Gln Asn Glu Gln Gly Ser Gly TyrAla Ala Asp Gln Lys Ser Thr 1 5 10 15 Gln Asn Ala Ile Asn Gly Ile ThrAsn Lys Val Asn Ser Val Ile Glu 20 25 30 Lys 216 34 PRT Influenza virus216 His Asn Gly Lys Ser Ser Phe Tyr Arg Asn Leu Leu Trp Leu Thr Glu 1 510 15 Lys Asn Gly Leu Tyr Pro Asn Leu Ser Lys Ser Tyr Val Asn Asn Lys 2025 30 Glu Lys 217 11 PRT Influenza virus 217 Lys His Phe Glu Lys Val LysIle Leu Pro Lys 1 5 10 218 14 PRT Influenza virus 218 Lys His Leu LeuSer Ser Val Lys His Phe Glu Lys Val Lys 1 5 10 219 13 PRT Influenzavirus MOD_RES (3) lys, gln or met 219 His Ala Xaa Xaa Ile Leu Glu LysThr His Asn Gly Lys 1 5 10 220 16 PRT Influenza virus MOD_RES (3) lys,gln or met 220 His Ala Xaa Xaa Ile Leu Glu Lys Thr His Asn Gly Lys LeuCys Xaa 1 5 10 15 221 19 PRT Influenza virus 221 His Asn Val His Pro LeuThr Ile Gly Glu Cys Pro Lys Tyr Val Lys 1 5 10 15 Ser Glu Lys 222 16 PRTInfluenza virus 222 His Pro Leu Thr Ile Gly Glu Cys Pro Lys Tyr Val LysSer Glu Lys 1 5 10 15 223 18 PRT Influenza virus 223 Lys His Leu Leu SerSer Val Lys His Phe Glu Lys Val Lys Ile Leu 1 5 10 15 Pro Lys 224 38 PRTInfluenza virus 224 Lys Arg Gln Ser Ser Gly Ile Met Lys Thr Glu Gly ThrLeu Glu Asn 1 5 10 15 Cys Glu Thr Lys Cys Gln Thr Pro Leu Gly Ala IleAsn Thr Thr Leu 20 25 30 Pro Phe His Asn Val His 35 225 27 PRT Influenzavirus MOD_RES (7) val or ile 225 Lys Gly Ser Asn Tyr Pro Xaa Ala Lys XaaSer Tyr Asn Asn Thr Ser 1 5 10 15 Gly Glu Gln Met Leu Ile Ile Trp GlnXaa His 20 25 226 36 PRT Influenza virus 226 His Thr Thr Leu Gly Gln SerArg Ala Cys Ala Val Ser Gly Asn Pro 1 5 10 15 Ser Phe Phe Arg Asn MetVal Trp Leu Thr Glu Lys Gly Ser Asn Tyr 20 25 30 Pro Val Ala Lys 35 2277 PRT Influenza virus 227 Lys His Phe Glu Lys Val Lys 1 5 228 38 PRTInfluenza virus 228 Lys Ile Ser Lys Arg Gly Ser Ser Gly Ile Met Lys ThrGlu Gly Thr 1 5 10 15 Leu Glu Asn Cys Glu Thr Lys Cys Gln Thr Pro LeuGly Ala Ile Asn 20 25 30 Thr Thr Leu Pro Phe His 35 229 35 PRT Influenzavirus 229 Lys Arg Gly Ser Ser Gly Ile Met Lys Thr Glu Gly Thr Leu GluAsn 1 5 10 15 Cys Glu Thr Lys Cys Gln Thr Pro Leu Gly Ala Ile Asn ThrThr Leu 20 25 30 Pro Phe His 35 230 27 PRT Influenza virus 230 Lys ThrGlu Gly Thr Leu Glu Asn Cys Glu Thr Lys Cys Gln Thr Pro 1 5 10 15 LeuGly Ala Ile Asn Thr Thr Leu Pro Phe His 20 25 231 38 PRT Influenza virus231 Lys Ile Ser Lys Arg Gly Ser Ser Gly Ile Met Lys Thr Glu Gly Thr 1 510 15 Leu Glu Asn Cys Glu Thr Lys Cys Gln Thr Pro Leu Gly Ala Ile Asn 2025 30 Thr Thr Leu Pro Phe His 35 232 30 PRT Influenza virus MOD_RES (29)val or ile 232 Lys Thr Glu Gly Thr Leu Glu Asn Cys Glu Thr Lys Cys GlnThr Pro 1 5 10 15 Leu Gly Ala Ile Asn Thr Thr Leu Pro Phe His Asn XaaHis 20 25 30 233 38 PRT Influenza virus 233 Lys Ile Ser Lys Arg Gly SerSer Gly Ile Met Lys Thr Glu Gly Thr 1 5 10 15 Leu Glu Asn Cys Glu ThrLys Cys Gln Thr Pro Leu Gly Ala Ile Asn 20 25 30 Thr Thr Leu Pro Phe His35 234 27 PRT Influenza virus MOD_RES (2) glu or gly 234 Lys Xaa Ser AsnTyr Pro Val Ala Lys Gly Ser Tyr Asn Asn Thr Ser 1 5 10 15 Gly Glu GlnMet Leu Ile Ile Trp Gly Val His 20 25 235 16 PRT Influenza virus 235 HisPro Leu Thr Ile Gly Glu Cys Pro Lys Tyr Val Lys Ser Glu Lys 1 5 10 15236 16 PRT Influenza virus 236 Lys Cys Gln Thr Pro Leu Gly Ala Ile LysThr Thr Leu Pro Phe His 1 5 10 15 237 58 PRT Influenza virus MOD_RES(21) phe or ile 237 His His Ser Asn Asp Gln Gly Ser Gly Tyr Ala Ala AspLys Glu Ser 1 5 10 15 Thr Gln Lys Ala Xaa Asp Gly Ile Thr Asn Lys ValAsn Ser Val Ile 20 25 30 Glu Lys Met Asn Thr Gln Phe Glu Ala Val Gly LysLeu Phe Xaa Asn 35 40 45 Leu Glu Lys Leu Glu Asn Leu Asn Lys Lys 50 55238 57 PRT Influenza virus MOD_RES (20) phe or ile 238 His Ser Asn AspGln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr 1 5 10 15 Gln Lys AlaXaa Asp Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu 20 25 30 Lys Met AsnThr Gln Phe Glu Ala Val Gly Lys Leu Phe Xaa Asn Leu 35 40 45 Glu Lys LeuGlu Asn Leu Asn Lys Lys 50 55 239 26 PRT Influenza virus MOD_RES (20)phe or ile 239 His Ser Asn Asp Gln Gly Ser Gly Tyr Ala Ala Asp Lys GluSer Thr 1 5 10 15 Gln Lys Ala Xaa Asp Gly Ile Thr Asn Lys 20 25 240 21PRT Influenza virus 240 His Asp Ser Asn Val Arg Asn Leu Tyr Asp Lys ValArg Met Gln Leu 1 5 10 15 Arg Asp Asn Ala Lys 20 241 30 PRT Influenzavirus 241 His Lys Cys Asp Asp Glu Cys Met Asn Ser Val Lys Asn Gly ThrTyr 1 5 10 15 Asp Tyr Pro Lys Leu Asn Arg Asn Glu Ile Lys Gly Val Lys 2025 30 242 27 PRT Influenza virus 242 His Lys Cys Asp Asp Glu Cys Met AsnSer Val Lys Asn Gly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys Leu Asn Arg AsnGlu Ile Lys 20 25 243 20 PRT Influenza virus 243 His Lys Cys Asp Asp GluCys Met Asn Ser Val Lys Asn Gly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys 20 24412 PRT Influenza virus 244 His Lys Cys Asp Asp Glu Cys Met Asn Ser ValLys 1 5 10 245 27 PRT Influenza virus 245 Lys Gly Ser Asn Tyr Pro ValAla Lys Gly Ser Tyr Asn Asn Thr Asn 1 5 10 15 Gly Glu Gln Ile Leu IleIle Trp Gly Val His 20 25 246 43 PRT Influenza virus 246 His Ser Asn AspGln Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr 1 5 10 15 Gln Lys AlaVal Asp Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu 20 25 30 Lys Met AsnThr Gln Phe Glu Ala Val Gly Lys 35 40 247 35 PRT Influenza virus 247 LysArg Gly Ser Ser Gly Ile Met Lys Thr Glu Gly Thr Leu Glu Asn 1 5 10 15Cys Glu Thr Lys Cys Gln Thr Pro Leu Gly Ala Ile Asn Thr Thr Leu 20 25 30Pro Phe His 35 248 16 PRT Influenza virus 248 His Pro Leu Thr Ile GlyGlu Cys Pro Lys Tyr Val Lys Ser Glu Lys 1 5 10 15 249 16 PRT Influenzavirus 249 His Ala Lys Asp Ile Leu Glu Lys Thr His Asn Gly Lys Leu CysLys 1 5 10 15 250 25 PRT Influenza virus 250 His Asp Val Tyr Arg Asp GluAla Leu Asn Asn Arg Phe Gln Ile Lys 1 5 10 15 Gly Val Glu Leu Lys SerGly Tyr Lys 20 25 251 19 PRT Influenza virus 251 His Thr Ile Asp Leu ThrAsp Ser Glu Met Asn Lys Leu Phe Glu Arg 1 5 10 15 Thr Arg Lys 252 7 PRTInfluenza virus 252 Lys Phe His Gln Ile Glu Lys 1 5 253 11 PRT Influenzavirus MOD_RES (8) gly or gln 253 Lys Thr Asn Glu Lys Phe His Xaa Ile GluLys 1 5 10 254 14 PRT Influenza virus MOD_RES (5) val or leu 254 Lys LeuAsn Arg Xaa Ile Glu Lys Thr Asn Glu Lys Phe His 1 5 10 255 25 PRTInfluenza virus 255 His Gln Ile Glu Lys Glu Phe Ser Glu Val Glu Gly ArgIle Gln Asp 1 5 10 15 Leu Glu Lys Tyr Val Glu Asp Thr Lys 20 25 256 8PRT Influenza virus 256 Lys Ile Cys Asn Asn Pro His Lys 1 5 257 14 PRTInfluenza virus 257 Lys Leu Asn Arg Val Ile Lys Lys Thr Asn Glu Lys PheHis 1 5 10 258 24 PRT Influenza virus MOD_RES (3) ile or val 258 His AspXaa Tyr Arg Asp Glu Ala Leu Asn Asn Arg Phe Gln Ile Lys 1 5 10 15 XaaVal Glu Xaa Ser Xaa Tyr Lys 20 259 25 PRT Influenza virus 259 His GlnIle Glu Lys Glu Phe Ser Glu Val Glu Gly Arg Ile Gln Asp 1 5 10 15 LeuGlu Lys Tyr Val Glu Asp Thr Lys 20 25 260 25 PRT Influenza virus 260 LysTyr Val Glu Asp Thr Lys Ile Asp Leu Trp Ser Tyr Asn Ala Glu 1 5 10 15Leu Leu Val Ala Leu Glu Asn Gln His 20 25 261 49 PRT Influenza virus 261Lys Tyr Val Lys Gln Asn Ser Leu Lys Leu Ala Thr Gly Met Arg Asn 1 5 1015 Val Pro Glu Lys Gln Thr Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe 20 2530 Ile Glu Asn Gly Trp Glu Gly Met Ile Asp Gly Trp Tyr Gly Phe Arg 35 4045 His 262 39 PRT Influenza virus 262 Lys Glu Phe Ser Glu Val Glu GlyArg Ile Gln Asp Leu Glu Lys Tyr 1 5 10 15 Val Glu Asp Thr Lys Ile AspLeu Trp Ser Tyr Asn Ala Glu Leu Leu 20 25 30 Val Ala Leu Glu Asn Gln His35 263 33 PRT Influenza virus MOD_RES (4) ser or glu 263 His Gln Asn XaaXaa Gly Xaa Gly Xaa Ala Ala Asp Xaa Lys Ser Thr 1 5 10 15 Gln Xaa AlaXaa Asp Xaa Ile Xaa Xaa Lys Xaa Asn Xaa Val Ile Xaa 20 25 30 Lys 264 18PRT Influenza virus MOD_RES (4) gly or gln 264 His Cys Asp Xaa Phe XaaAsn Glu Lys Trp Asp Leu Phe Xaa Glu Arg 1 5 10 15 Xaa Lys 265 20 PRTInfluenza virus 265 His Thr Ile Asp Leu Thr Asp Ser Glu Met Asn Lys LysLeu Phe Glu 1 5 10 15 Arg Thr Arg Lys 20 266 28 PRT Influenza virus 266Lys Ser Gly Ser Thr Tyr Pro Val Leu Lys Val Thr Met Pro Asn Asn 1 5 1015 Asp Asn Phe Asp Lys Leu Tyr Ile Trp Gly Val His 20 25 267 34 PRTInfluenza virus 267 Lys Leu Asn Trp Leu Thr Lys Ser Gly Asn Thr Tyr ProVal Leu Asn 1 5 10 15 Val Thr Met Pro Asn Asn Asp Asn Phe Asp Lys LeuVal Ile Trp Gly 20 25 30 Val His 268 19 PRT Influenza virus 268 His ThrIle Asp Leu Thr Asp Ser Glu Met Asn Lys Leu Phe Glu Lys 1 5 10 15 ThrArg Lys 269 18 PRT Influenza virus 269 Lys Leu Asn Arg Leu Ile Glu LysThr Asn Glu Lys Phe His Gln Thr 1 5 10 15 Glu Lys 270 47 PRT Influenzavirus 270 His Thr Gly Lys Ser Ser Val Met Arg Ser Asp Ala Pro Ile AspPhe 1 5 10 15 Cys Asn Ser Glu Cys Ile Thr Pro Asn Gln Ser Ile Pro AsnAsp Lys 20 25 30 Pro Phe Gln Asn Val Asn Lys Ile Thr Tyr Gly Ala Cys ProLys 35 40 45 271 39 PRT Influenza virus 271 His Thr Gly Lys Ser Ser ValMet Arg Ser Asp Ala Pro Ile Asp Phe 1 5 10 15 Cys Asn Ser Glu Cys IleThr Pro Asn Gln Ser Ile Pro Asn Asp Lys 20 25 30 Pro Phe Gln Asn Val AsnLys 35 272 33 PRT Influenza virus 272 His Pro Ser Thr Asp Ser Asp GlnThr Ser Leu Tyr Val Arg Ala Ser 1 5 10 15 Gly Arg Val Thr Val Ser ThrLys Arg Ser Gln Gln Thr Val Ile Pro 20 25 30 Lys 273 25 PRT Influenzavirus 273 Lys Tyr Val Glu Asp Thr Lys Ile Asp Leu Trp Ser Tyr Asn AlaGlu 1 5 10 15 Leu Leu Val Ala Leu Glu Asn Gln His 20 25 274 26 PRTInfluenza virus 274 Lys Leu Phe Glu Arg Thr Arg Lys Gln Leu Arg Glu AsnAla Glu Asp 1 5 10 15 Met Gly Asn Gly Cys Phe Lys Ile Tyr His 20 25 27516 PRT Influenza virus 275 Lys Arg Arg Ser Ile Lys Ser Phe Phe Ser ArgLeu Asn Trp Leu His 1 5 10 15 276 16 PRT Influenza virus MOD_RES (12)val or arg 276 His Pro Val Thr Ile Gly Glu Cys Pro Lys Tyr Xaa Lys SerThr Lys 1 5 10 15 277 30 PRT Influenza virus 277 Lys Gly Asn Ser Tyr ProLys Leu Ser Lys Leu Ser Lys Ser Tyr Ile 1 5 10 15 Ile Asn Lys Lys LysGlu Val Leu Val Ile Trp Gly Ile His 20 25 30 278 24 PRT Influenza virusMOD_RES (9) val or tyr 278 Lys Leu Ser Lys Leu Ser Lys Ser Xaa Ile IleAsn Lys Lys Lys Glu 1 5 10 15 Val Leu Val Ile Trp Gly Ile His 20 279 21PRT Influenza virus MOD_RES (6) val or tyr 279 Lys Leu Ser Lys Ser XaaIle Ile Asn Lys Lys Lys Glu Val Leu Val 1 5 10 15 Ile Trp Gly Ile His 20280 46 PRT Plasmodium falciparum 280 Lys Glu Glu Glu Glu Lys Glu Lys GluLys Glu Lys Glu Lys Glu Glu 1 5 10 15 Lys Glu Lys Glu Glu Lys Glu LysGlu Glu Lys Glu Lys Glu Lys Glu 20 25 30 Glu Lys Glu Lys Glu Lys Glu GluLys Glu Glu Glu Lys Lys 35 40 45 281 48 PRT Plasmodium falciparum 281Lys Glu Glu Glu Glu Lys Glu Lys Glu Lys Glu Lys Glu Lys Glu Glu 1 5 1015 Lys Glu Lys Glu Glu Lys Glu Lys Glu Glu Lys Glu Lys Glu Lys Glu 20 2530 Glu Lys Glu Lys Glu Lys Glu Glu Lys Glu Glu Glu Lys Lys Glu Lys 35 4045 282 47 PRT Plasmodium falciparum 282 Lys Glu Glu Glu Glu Lys Glu LysGlu Lys Glu Lys Glu Lys Glu Glu 1 5 10 15 Lys Glu Lys Glu Glu Lys GluLys Glu Lys Glu Glu Lys Glu Lys Glu 20 25 30 Glu Lys Glu Lys Glu Glu LysGlu Glu Lys Glu Glu Glu Lys Lys 35 40 45 283 10 PRT Plasmodiumfalciparum 283 Lys Glu Glu Glu Glu Lys Glu Lys Glu Lys 1 5 10 284 19 PRTPlasmodium falciparum 284 His Lys Lys Leu Ile Lys Ala Leu Lys Lys AsnIle Glu Ser Ile Gln 1 5 10 15 Asn Lys Lys 285 19 PRT Plasmodiumfalciparum 285 His Lys Lys Leu Ile Lys Ala Leu Lys Lys Asn Ile Glu SerIle Gln 1 5 10 15 Asn Lys Met 286 10 PRT Plasmodium falciparum 286 HisLys Lys Leu Ile Lys Ala Leu Lys Lys 1 5 10 287 9 PRT Plasmodiumfalciparum 287 His Lys Lys Leu Ile Lys Ala Leu Lys 1 5 288 23 PRTPlasmodium falciparum 288 Lys Ala Thr Tyr Ser Phe Val Asn Thr Lys LysLys Ile Ile Ser Leu 1 5 10 15 Lys Ser Gln Gly His Lys Lys 20 289 22 PRTPlasmodium falciparum 289 Lys Ala Thr Tyr Ser Phe Val Asn Thr Lys LysLys Ile Ile Ser Leu 1 5 10 15 Lys Ser Gln Gly His Lys 20 290 21 PRTPlasmodium falciparum 290 Lys Ala Thr Tyr Ser Phe Val Asn Thr Lys LysLys Ile Ile Ser Leu 1 5 10 15 Lys Ser Gln Gly His 20 291 29 PRTPlasmodium falciparum 291 His Thr Tyr Val Lys Gly Lys Lys Ala Pro SerAsp Pro Gln Cys Ala 1 5 10 15 Asp Ile Lys Glu Glu Cys Lys Glu Leu LeuLys Glu Lys 20 25 292 11 PRT Plasmodium falciparum 292 Lys Ile Ile SerLeu Lys Ser Gln Gly His Lys 1 5 10 293 21 PRT Plasmodium falciparum 293Lys Lys Lys Lys Phe Glu Pro Leu Lys Asn Gly Asn Val Ser Glu Thr 1 5 1015 Ile Lys Leu Ile His 20 294 20 PRT Plasmodium falciparum 294 Lys LysLys Phe Glu Pro Leu Lys Asn Gly Asn Val Ser Glu Thr Ile 1 5 10 15 LysLeu Ile His 20 295 19 PRT Plasmodium falciparum 295 Lys Lys Phe Glu ProLeu Lys Asn Gly Asn Val Ser Glu Thr Ile Lys 1 5 10 15 Leu Ile His 296 13PRT Plasmodium falciparum 296 Lys Asn Gly Asn Val Ser Glu Thr Ile LysLeu Ile His 1 5 10 297 11 PRT Plasmodium falciparum 297 Lys Leu Ile HisLeu Gly Asn Lys Asp Lys Lys 1 5 10 298 36 PRT Plasmodium falciparum 298Lys Val Lys Lys Ile Gly Val Thr Leu Lys Lys Phe Glu Pro Leu Lys 1 5 1015 Asn Gly Asn Val Ser Glu Thr Ile Lys Leu Ile His Leu Gly Asn Lys 20 2530 Asp Lys Lys His 35 299 59 PRT Plasmodium falciparum 299 His Leu IleTyr Lys Asn Lys Ser Tyr Asn Pro Leu Leu Leu Ser Cys 1 5 10 15 Val LysLys Met Asn Met Leu Lys Glu Asn Val Asp Tyr Ile Gln Asn 20 25 30 Gln AsnLeu Phe Lys Glu Leu Met Asn Gln Lys Ala Thr Tyr Ser Phe 35 40 45 Val AsnThr Lys Lys Lys Ile Ile Ser Leu Lys 50 55 300 52 PRT Plasmodiumfalciparum 300 His Leu Ile Tyr Lys Asn Lys Ser Tyr Asn Pro Leu Leu LeuSer Cys 1 5 10 15 Val Lys Lys Met Asn Met Leu Lys Glu Asn Val Asp TyrIle Gln Asn 20 25 30 Gln Asn Leu Phe Lys Glu Leu Met Asn Gln Lys Ala ThrTyr Ser Phe 35 40 45 Val Asn Thr Lys 50 301 43 PRT Plasmodium falciparum301 His Leu Ile Tyr Lys Asn Lys Ser Tyr Asn Pro Leu Leu Leu Ser Cys 1 510 15 Val Lys Lys Met Asn Met Leu Lys Glu Asn Val Asp Tyr Ile Gln Asn 2025 30 Gln Asn Leu Phe Lys Glu Leu Met Asn Gln Lys 35 40 302 38 PRTPlasmodium falciparum 302 His Leu Ile Tyr Lys Asn Lys Ser Tyr Asn ProLeu Leu Leu Ser Cys 1 5 10 15 Val Lys Lys Met Asn Met Leu Lys Glu AsnVal Asp Tyr Ile Gln Lys 20 25 30 Asn Gln Asn Leu Phe Lys 35 303 24 PRTPlasmodium falciparum 303 His Leu Ile Tyr Lys Asn Lys Ser Tyr Asn ProLeu Leu Leu Ser Cys 1 5 10 15 Val Lys Lys Met Asn Met Leu Lys 20 304 47PRT Plasmodium falciparum 304 Lys Ser Ala Asn Asn Ser Ala Asn Asn GlyLys Lys Asn Asn Ala Glu 1 5 10 15 Glu Met Lys Asn Leu Val Asn Phe LeuGln Ser His Lys Lys Leu Ile 20 25 30 Lys Ala Leu Lys Lys Asn Ile Glu SerIle Gln Asn Lys Lys His 35 40 45 305 37 PRT Plasmodium falciparum 305Lys Lys Asn Asn Ala Glu Glu Met Lys Asn Leu Val Asn Phe Leu Gln 1 5 1015 Ser His Lys Lys Leu Ile Lys Ala Leu Lys Lys Asn Ile Glu Ser Ile 20 2530 Gln Asn Lys Lys His 35 306 29 PRT Plasmodium falciparum 306 Lys AsnLeu Val Asn Phe Leu Gln Ser His Lys Lys Leu Ile Lys Ala 1 5 10 15 LeuLys Lys Asn Ile Glu Ser Ile Gln Asn Lys Lys His 20 25 307 19 PRTPlasmodium falciparum 307 Lys Lys Leu Ile Lys Ala Leu Lys Lys Asn IleGlu Ser Ile Gln Asn 1 5 10 15 Lys Lys His 308 18 PRT Plasmodiumfalciparum 308 Lys Leu Ile Lys Ala Leu Lys Lys Asn Ile Glu Ser Ile GlnAsn Lys 1 5 10 15 Lys His 309 12 PRT Plasmodium falciparum 309 Lys LysAsn Ile Glu Ser Ile Gln Asn Lys Lys His 1 5 10 310 11 PRT Plasmodiumfalciparum 310 Lys Asn Ile Glu Ser Ile Gln Asn Lys Lys His 1 5 10 311 17PRT Plasmodium falciparum 311 Lys Asn Asn Ala Glu Glu Met Lys Asn LeuVal Asn Phe Leu Gln Ser 1 5 10 15 His 312 23 PRT Plasmodium falciparum312 Lys Lys Leu Ile Lys Ala Leu Lys Lys Asn Ile Glu Ser Ile Gln Asn 1 510 15 Lys Lys Gln Gly His Lys Lys 20 313 19 PRT Plasmodium falciparum313 Lys Lys Asn Asn Ala Glu Glu Met Lys Asn Leu Val Asn Phe Leu Gln 1 510 15 Ser His Lys 314 17 PRT Plasmodium falciparum 314 Lys Asn Asn AlaGlu Glu Met Lys Asn Leu Val Asn Phe Leu Gln Ser 1 5 10 15 His 315 22 PRTPlasmodium falciparum 315 Lys Leu Ile Lys Ala Leu Lys Lys Asn Ile GluSer Ile Gln Asn Lys 1 5 10 15 Lys Gln Gly His Lys Lys 20 316 28 PRTPlasmodium falciparum 316 Lys Val Lys Lys Ile Gly Val Thr Leu Lys LysPhe Glu Pro Leu Lys 1 5 10 15 Asn Gly Asn Val Ser Glu Thr Ile Lys LeuIle His 20 25 317 13 PRT Plasmodium falciparum 317 Lys Asn Gly Asn ValSer Glu Thr Ile Lys Leu Ile His 1 5 10 318 11 PRT Plasmodium falciparum318 Lys Leu Ile His Leu Gly Asn Lys Asp Lys Lys 1 5 10 319 28 PRTPlasmodium falciparum 319 Lys Ser Ala Asn Asn Ser Ala Asn Asn Gly LysLys Asn Asn Ala Glu 1 5 10 15 Glu Met Lys Asn Leu Val Asn Phe Leu GlnSer His 20 25 320 18 PRT Plasmodium falciparum 320 Lys Lys Asn Asn AlaGlu Glu Met Lys Asn Leu Val Asn Phe Leu Gln 1 5 10 15 Ser His 321 19 PRTPlasmodium falciparum 321 Lys Lys Leu Ile Lys Ala Leu Lys Lys Asn IleGlu Ser Ile Gln Asn 1 5 10 15 Lys Lys His 322 15 PRT Plasmodiumfalciparum 322 Lys Ala Leu Lys Lys Asn Ile Glu Ser Ile Gln Asn Lys LysHis 1 5 10 15 323 12 PRT Plasmodium falciparum 323 Lys Lys Asn Ile GluSer Ile Gln Asn Lys Lys His 1 5 10 324 27 PRT Plasmodium falciparum 324Lys Glu Leu Met Asn Gln Lys Ala Thr Tyr Ser Phe Val Asn Thr Lys 1 5 1015 Lys Lys Ile Ile Ser Leu Lys Ser Gln Gly His 20 25 325 7 PRTPlasmodium falciparum 325 Lys Ser Gln Gly His Lys Lys 1 5 326 12 PRTPlasmodium falciparum 326 Lys Lys Lys Ile Ile Ser Leu Lys Ser Gln GlyHis 1 5 10 327 11 PRT Plasmodium falciparum 327 Lys Lys Ile Ile Ser LeuLys Ser Gln Gly His 1 5 10 328 12 PRT Plasmodium falciparum 328 Lys LysAsn Ile Glu Ser Ile Gln Asn Lys Lys His 1 5 10 329 11 PRT Plasmodiumfalciparum 329 Lys Asn Ile Glu Ser Ile Gln Asn Lys Lys His 1 5 10 330 29PRT Plasmodium falciparum 330 His Thr Tyr Val Lys Gly Lys Lys Ala ProSer Asp Pro Gln Cys Ala 1 5 10 15 Asp Ile Lys Glu Glu Cys Lys Glu LeuLeu Lys Glu Lys 20 25 331 27 PRT Plasmodium falciparum 331 His Thr TyrVal Lys Gly Lys Lys Ala Pro Ser Asp Pro Gln Cys Ala 1 5 10 15 Asp IleLys Glu Glu Cys Lys Glu Leu Leu Lys 20 25 332 29 PRT Plasmodiumfalciparum 332 His Glu Asn Val Leu Ser Ala Ala Leu Glu Asn Thr Gln SerGlu Glu 1 5 10 15 Glu Lys Lys Glu Val Ile Asp Val Ile Glu Glu Val Lys 2025 333 48 PRT Plasmodium falciparum 333 Lys Glu Asn Val Val Thr Thr IleLeu Glu Lys Val Glu Glu Thr Thr 1 5 10 15 Ala Glu Ser Val Thr Thr PheSer Asn Ile Leu Glu Glu Ile Gln Glu 20 25 30 Asn Thr Ile Thr Asn Asp ThrIle Glu Glu Lys Leu Glu Glu Leu His 35 40 45 334 14 PRT Plasmodiumfalciparum 334 His Tyr Leu Gln Gln Met Lys Glu Lys Phe Ser Lys Glu Lys 15 10 335 42 PRT Plasmodium falciparum 335 His Tyr Leu Gln Gln Met LysGlu Lys Phe Ser Lys Glu Lys Asn Asn 1 5 10 15 Asn Val Ile Glu Val ThrAsn Lys Ala Glu Lys Lys Gly Asn Val Gln 20 25 30 Val Thr Asn Lys Thr GluLys Thr Thr Lys 35 40 336 48 PRT Plasmodium falciparum 336 His Tyr LeuGln Gln Met Lys Glu Lys Phe Ser Lys Glu Lys Asn Asn 1 5 10 15 Asn ValIle Glu Val Thr Asn Lys Ala Glu Lys Lys Gly Asn Val Gln 20 25 30 Val ThrAsn Lys Thr Glu Lys Thr Thr Lys Val Asp Lys Asn Asn Lys 35 40 45 337 57PRT Plasmodium falciparum 337 His Tyr Leu Gln Gln Met Lys Glu Lys PheSer Lys Glu Lys Asn Asn 1 5 10 15 Asn Val Ile Glu Val Thr Asn Lys AlaGlu Lys Lys Gly Asn Val Gln 20 25 30 Val Thr Asn Lys Thr Glu Lys Thr ThrLys Val Asp Lys Asn Asn Lys 35 40 45 Val Pro Lys Lys Arg Arg Thr Gln Lys50 55 338 59 PRT Plasmodium falciparum 338 His Tyr Leu Gln Gln Met LysGlu Lys Phe Ser Lys Glu Lys Asn Asn 1 5 10 15 Asn Val Ile Glu Val ThrAsn Lys Ala Glu Lys Lys Gly Asn Val Gln 20 25 30 Val Thr Asn Lys Thr GluLys Thr Thr Lys Val Asp Lys Asn Asn Lys 35 40 45 Val Pro Lys Lys Arg ArgThr Gln Lys Ser Lys 50 55 339 52 PRT Plasmodium falciparum 339 His ValAsp Glu Val Met Lys Tyr Val Gln Lys Ile Asp Lys Glu Val 1 5 10 15 AspLys Glu Val Ser Lys Ala Leu Glu Ser Lys Asn Asp Val Thr Asn 20 25 30 ValLeu Lys Gln Asn Gln Asp Phe Phe Ser Lys Val Lys Asn Phe Val 35 40 45 LysLys Tyr Lys 50 340 50 PRT Plasmodium falciparum 340 His Val Asp Glu ValMet Lys Tyr Val Gln Lys Ile Asp Lys Glu Val 1 5 10 15 Asp Lys Glu ValSer Lys Ala Leu Glu Ser Lys Asn Asp Val Thr Asn 20 25 30 Val Leu Lys GlnAsn Gln Asp Phe Phe Ser Lys Val Lys Asn Phe Val 35 40 45 Lys Lys 50 34143 PRT Plasmodium falciparum 341 His Val Asp Glu Val Met Lys Tyr Val GlnLys Ile Asp Lys Glu Val 1 5 10 15 Asp Lys Glu Val Ser Lys Ala Leu GluSer Lys Asn Asp Val Thr Asn 20 25 30 Val Leu Lys Gln Asn Gln Asp Phe PheSer Lys 35 40 342 35 PRT Plasmodium falciparum 342 His Val Asp Glu ValMet Lys Tyr Val Gln Lys Ile Asp Lys Glu Val 1 5 10 15 Asp Lys Glu ValSer Lys Ala Leu Glu Ser Lys Asn Asp Val Thr Asn 20 25 30 Val Leu Lys 35343 27 PRT Plasmodium falciparum 343 His Val Asp Glu Val Met Lys Tyr ValGln Lys Ile Asp Lys Glu Val 1 5 10 15 Asp Lys Glu Val Ser Lys Ala LeuGlu Ser Lys 20 25 344 22 PRT Plasmodium falciparum 344 His Val Asp GluVal Met Lys Tyr Val Gln Lys Ile Asp Lys Glu Val 1 5 10 15 Asp Lys GluVal Ser Lys 20 345 18 PRT Plasmodium falciparum 345 His Val Asp Glu ValMet Lys Tyr Val Gln Lys Ile Asp Lys Glu Val 1 5 10 15 Asp Lys 346 14 PRTPlasmodium falciparum 346 His Val Asp Glu Val Met Lys Tyr Val Gln LysIle Asp Lys 1 5 10 347 39 PRT Plasmodium falciparum 347 Lys Asp Glu ValIle Asp Leu Ile Val Gln Lys Glu Lys Arg Ile Glu 1 5 10 15 Lys Val LysAla Lys Lys Lys Lys Leu Glu Lys Lys Val Glu Glu Gly 20 25 30 Val Ser GlyLeu Lys Lys His 35 348 23 PRT Plasmodium falciparum 348 Lys Val Lys AlaLys Lys Lys Lys Leu Glu Lys Lys Val Glu Glu Gly 1 5 10 15 Val Ser GlyLeu Lys Lys His 20 349 21 PRT Plasmodium falciparum 349 Lys Ala Lys LysLys Lys Leu Glu Lys Lys Val Glu Glu Gly Val Ser 1 5 10 15 Gly Leu LysLys His 20 350 19 PRT Plasmodium falciparum 350 Lys Lys Lys Lys Leu GluLys Lys Val Glu Glu Gly Val Ser Gly Leu 1 5 10 15 Lys Lys His 351 18 PRTPlasmodium falciparum 351 Lys Lys Lys Leu Glu Lys Lys Val Glu Glu GlyVal Ser Gly Leu Lys 1 5 10 15 Lys His 352 17 PRT Plasmodium falciparum352 Lys Lys Leu Glu Lys Lys Val Glu Glu Gly Val Ser Gly Leu Lys Lys 1 510 15 His 353 16 PRT Plasmodium falciparum 353 Lys Leu Glu Lys Lys ValGlu Glu Gly Val Ser Gly Leu Lys Lys His 1 5 10 15 354 13 PRT Plasmodiumfalciparum 354 Lys Lys Val Glu Glu Gly Val Ser Gly Leu Lys Lys His 1 510 355 12 PRT Plasmodium falciparum 355 Lys Val Glu Glu Gly Val Ser GlyLeu Lys Lys His 1 5 10 356 59 PRT Plasmodium falciparum 356 His Val GluGln Asn Val Tyr Val Asp Val Asp Val Pro Ala Met Lys 1 5 10 15 Asp GlnPhe Leu Gly Ile Leu Asn Glu Ala Gly Gly Leu Lys Glu Met 20 25 30 Phe PheAsn Leu Glu Asp Val Phe Lys Ser Glu Ser Asp Val Ile Thr 35 40 45 Val GluGlu Ile Lys Asp Glu Pro Val Gln Lys 50 55 357 53 PRT Plasmodiumfalciparum 357 His Ile Lys Gly Leu Glu Glu Asp Asp Leu Glu Glu Val AspAsp Leu 1 5 10 15 Lys Gly Ser Ile Leu Asp Met Leu Lys Gly Asp Met GluLeu Gly Asp 20 25 30 Met Asp Lys Glu Ser Leu Glu Asp Val Thr Thr Lys LeuGly Glu Arg 35 40 45 Val Glu Ser Leu Lys 50 358 44 PRT Plasmodiumfalciparum 358 His Ile Lys Gly Leu Glu Glu Asp Asp Leu Glu Glu Val AspAsp Leu 1 5 10 15 Lys Gly Ser Ile Leu Asp Met Leu Lys Gly Asp Met GluLeu Gly Asp 20 25 30 Met Asp Lys Glu Ser Leu Glu Asp Val Thr Thr Lys 3540 359 35 PRT Plasmodium falciparum 359 His Ile Lys Gly Leu Glu Glu AspAsp Leu Glu Glu Val Asp Asp Leu 1 5 10 15 Lys Gly Ser Ile Leu Asp MetLeu Lys Gly Asp Met Glu Leu Gly Asp 20 25 30 Met Asp Lys 35 360 25 PRTPlasmodium falciparum 360 His Ile Lys Gly Leu Glu Glu Asp Asp Leu GluGlu Val Asp Asp Leu 1 5 10 15 Lys Gly Ser Ile Leu Asp Met Leu Lys 20 25361 31 PRT Plasmodium falciparum 361 His Ile Ile Ser Gly Asp Ala Asp ValLeu Ser Ser Ala Leu Gly Met 1 5 10 15 Asp Glu Glu Gln Met Lys Thr ArgLys Lys Ala Gln Arg Pro Lys 20 25 30 362 23 PRT Plasmodium falciparum362 His Asp Ile Thr Thr Thr Leu Asp Glu Val Val Glu Leu Lys Asp Val 1 510 15 Glu Glu Asp Lys Ile Glu Lys 20 363 10 PRT Plasmodium falciparum363 Lys Lys Leu Glu Glu Val His Glu Leu Lys 1 5 10 364 9 PRT Plasmodiumfalciparum 364 Lys Leu Glu Glu Val His Glu Leu Lys 1 5 365 19 PRTPlasmodium falciparum 365 Lys Thr Ile Glu Thr Asp Ile Leu Glu Glu LysLys Lys Glu Ile Glu 1 5 10 15 Lys Asp His 366 11 PRT Plasmodiumfalciparum 366 Lys Lys Glu Ile Glu Lys Asp His Phe Glu Lys 1 5 10 367 6PRT Plasmodium falciparum 367 Lys Asp His Phe Glu Lys 1 5 368 11 PRTPlasmodium falciparum 368 Lys Phe Glu Glu Glu Ala Glu Glu Ile Lys His 15 10 369 47 PRT Plasmodium falciparum 369 Lys Asp Gly Asp Thr Lys CysThr Leu Glu Cys Ala Gln Gly Lys Lys 1 5 10 15 Cys Ile Lys His Lys SerAsp His Asn His Lys Ser Asp His Asn His 20 25 30 Lys Ser Asp Pro Asn HisLys Lys Lys Asn Asn Asn Asn Asn Lys 35 40 45 370 40 PRT Plasmodiumfalciparum 370 Lys Asp Gly Asp Thr Lys Cys Thr Leu Glu Cys Ala Gln GlyLys Lys 1 5 10 15 Cys Ile Lys His Lys Ser Asp His Asn His Lys Ser AspHis Asn His 20 25 30 Lys Ser Asp Pro Asn His Lys Lys 35 40 371 39 PRTPlasmodium falciparum 371 Lys Asp Gly Asp Thr Lys Cys Thr Leu Glu CysAla Gln Gly Lys Lys 1 5 10 15 Cys Ile Lys His Lys Ser Asp His Asn HisLys Ser Asp His Asn His 20 25 30 Lys Ser Asp Pro Asn His Lys 35 372 33PRT Plasmodium falciparum 372 Lys Asp Gly Asp Thr Lys Cys Thr Leu GluCys Ala Gln Gly Lys Lys 1 5 10 15 Cys Ile Lys His Lys Ser Asp His AsnHis Lys Ser Asp His Asn His 20 25 30 Lys 373 27 PRT Plasmodiumfalciparum 373 Lys Asp Gly Asp Thr Lys Cys Thr Leu Glu Cys Ala Gln GlyLys Lys 1 5 10 15 Cys Ile Lys His Lys Ser Asp His Asn His Lys 20 25 37421 PRT Plasmodium falciparum 374 Lys Asp Gly Asp Thr Lys Cys Thr Leu GluCys Ala Gln Gly Lys Lys 1 5 10 15 Cys Ile Lys His Lys 20 375 16 PRTPlasmodium falciparum 375 Lys Asp Gly Asp Thr Lys Cys Thr Leu Glu CysAla Gln Gly Lys Lys 1 5 10 15 376 15 PRT Plasmodium falciparum 376 LysAsp Gly Asp Thr Lys Cys Thr Leu Glu Cys Ala Gln Gly Lys 1 5 10 15 377 23PRT Plasmodium falciparum 377 Lys Cys Ile Gln Ala Glu Cys Asn Tyr LysGlu Cys Gly Glu Gln Lys 1 5 10 15 Cys Val Trp Asp Gly Ile His 20 378 14PRT Plasmodium falciparum 378 Lys Glu Cys Gly Glu Gln Lys Cys Val TrpAsp Gly Ile His 1 5 10 379 32 PRT Plasmodium falciparum 379 His Ile GluCys Lys Cys Asn Asn Asp Tyr Val Leu Thr Asn Arg Tyr 1 5 10 15 Glu CysGlu Pro Lys Asn Lys Cys Thr Ser Leu Glu Asp Thr Asn Lys 20 25 30 380 39PRT Plasmodium falciparum 380 Lys Ser Asp His Asn His Lys Ser Asp HisAsn His Lys Ser Asp His 1 5 10 15 Asn His Lys Ser Asp His Asn His LysSer Asp Pro Asn His Lys Lys 20 25 30 Lys Asn Asn Asn Asn Asn Lys 35 38133 PRT Plasmodium falciparum 381 Lys Ser Asp His Asn His Lys Ser Asp HisAsn His Lys Ser Asp His 1 5 10 15 Asn His Lys Ser Asp Pro Asn His LysLys Lys Asn Asn Asn Asn Asn 20 25 30 Lys 382 27 PRT Plasmodiumfalciparum 382 Lys Ser Asp His Asn His Lys Ser Asp His Asn His Lys SerAsp Pro 1 5 10 15 Asn His Lys Lys Lys Asn Asn Asn Asn Asn Lys 20 25 38321 PRT Plasmodium falciparum 383 Lys Ser Asp His Asn His Lys Ser Asp ProAsn His Lys Lys Lys Asn 1 5 10 15 Asn Asn Asn Asn Lys 20 384 18 PRTPlasmodium falciparum 384 Lys Lys Lys Asn Asn Asn Asn Asn Lys Asp AsnLys Ser Asp Pro Asn 1 5 10 15 His Lys 385 17 PRT Plasmodium falciparum385 Lys Lys Asn Asn Asn Asn Asn Lys Asp Asn Lys Ser Asp Pro Asn His 1 510 15 Lys 386 16 PRT Plasmodium falciparum 386 Lys Asn Asn Asn Asn AsnLys Asp Asn Lys Ser Asp Pro Asn His Lys 1 5 10 15 387 10 PRT Plasmodiumfalciparum 387 Lys Asp Asn Lys Ser Asp Pro Asn His Lys 1 5 10 388 7 PRTPlasmodium falciparum 388 Lys Ser Asp Pro Asn His Lys 1 5 389 35 PRTPlasmodium falciparum 389 His Ser Leu Tyr Ala Leu Gln Gln Asn Glu GluTyr Gln Lys Val Lys 1 5 10 15 Asn Glu Lys Asp Gln Asn Glu Ile Lys LysIle Lys Gln Leu Ile Glu 20 25 30 Lys Asn Lys 35 390 28 PRT Plasmodiumfalciparum 390 His Ser Leu Tyr Ala Leu Gln Gln Asn Glu Glu Tyr Gln LysVal Lys 1 5 10 15 Asn Glu Lys Asp Gln Asn Glu Ile Lys Lys Ile Lys 20 25391 26 PRT Plasmodium falciparum 391 His Ser Leu Tyr Ala Leu Gln Gln AsnGlu Glu Tyr Gln Lys Val Lys 1 5 10 15 Asn Glu Lys Asp Gln Asn Glu IleLys Lys 20 25 392 25 PRT Plasmodium falciparum 392 His Ser Leu Tyr AlaLeu Gln Gln Asn Glu Glu Tyr Gln Lys Val Lys 1 5 10 15 Asn Glu Lys AspGln Asn Glu Ile Lys 20 25 393 11 PRT Plasmodium falciparum 393 His LysLeu Glu Asn Leu Glu Glu Met Asp Lys 1 5 10 394 11 PRT Plasmodiumfalciparum 394 Lys His Phe Asp Asp Asn Thr Asn Glu Gln Lys 1 5 10 395 8PRT Plasmodium falciparum 395 Lys Lys Glu Asp Asp Glu Lys His 1 5 396 13PRT Plasmodium falciparum 396 Lys Glu Glu Asn Asn Lys Lys Glu Asp AspGlu Lys His 1 5 10 397 21 PRT Plasmodium falciparum 397 Lys Thr Ser SerGly Ile Leu Asn Lys Glu Glu Asn Asn Lys Lys Glu 1 5 10 15 Asp Asp GluLys His 20 398 7 PRT Plasmodium falciparum 398 Lys Asn Ile His Ile LysLys 1 5 399 13 PRT Plasmodium falciparum 399 His Ile Lys Lys Lys Glu GlyIle Asp Ile Gly Tyr Lys 1 5 10 400 21 PRT Plasmodium falciparum 400 LysLys Met Trp Thr Cys Lys Leu Trp Asp Asn Lys Gly Asn Glu Ile 1 5 10 15Thr Lys Asn Ile His 20 401 30 PRT Plasmodium falciparum 401 Lys Lys GlyIle Gln Trp Asn Leu Leu Lys Lys Met Trp Thr Cys Lys 1 5 10 15 Leu TrpAsp Asn Lys Gly Asn Glu Ile Thr Lys Asn Ile His 20 25 30 402 50 PRTPlasmodium falciparum 402 Lys Glu Lys Lys Asp Ser Asn Glu Asn Arg LysLys Lys Gln Lys Glu 1 5 10 15 Asp Lys Lys Asn Pro Asn Lys Leu Lys LysIle Glu Tyr Thr Asn Lys 20 25 30 Ile Thr His Phe Phe Lys Ala Lys Asn AsnLys Gln Gln Asn Asn Val 35 40 45 Thr His 50 403 48 PRT Plasmodiumfalciparum 403 Lys Lys Asp Ser Asn Glu Asn Arg Lys Lys Lys Gln Lys GluAsp Lys 1 5 10 15 Lys Asn Pro Asn Lys Leu Lys Lys Ile Glu Tyr Thr AsnLys Ile Thr 20 25 30 His Phe Phe Lys Ala Lys Asn Asn Lys Gln Gln Asn AsnVal Thr His 35 40 45 404 47 PRT Plasmodium falciparum 404 Lys Asp SerAsn Glu Asn Arg Lys Lys Lys Gln Lys Glu Asp Lys Lys 1 5 10 15 Asn ProAsn Lys Leu Lys Lys Ile Glu Tyr Thr Asn Lys Ile Thr His 20 25 30 Phe PheLys Ala Lys Asn Asn Lys Gln Gln Asn Asn Val Thr His 35 40 45 405 39 PRTPlasmodium falciparum 405 Lys Lys Gln Lys Glu Asp Lys Lys Asn Pro AsnLys Leu Lys Lys Ile 1 5 10 15 Glu Tyr Thr Asn Lys Ile Thr His Phe PheLys Ala Lys Asn Asn Lys 20 25 30 Gln Gln Asn Asn Val Thr His 35 406 38PRT Plasmodium falciparum 406 Lys Gln Lys Glu Asp Lys Lys Asn Pro AsnLys Leu Lys Lys Ile Glu 1 5 10 15 Tyr Thr Asn Lys Ile Thr His Phe PheLys Ala Lys Asn Asn Lys Gln 20 25 30 Gln Asn Asn Val Thr His 35 407 36PRT Plasmodium falciparum 407 Lys Glu Asp Lys Lys Asn Pro Asn Lys LeuLys Lys Ile Glu Tyr Thr 1 5 10 15 Asn Lys Ile Thr His Phe Phe Lys AlaLys Asn Asn Lys Gln Gln Asn 20 25 30 Asn Val Thr His 35 408 32 PRTPlasmodium falciparum 408 Lys Asn Pro Asn Lys Leu Lys Lys Ile Glu TyrThr Asn Lys Ile Thr 1 5 10 15 His Phe Phe Lys Ala Lys Asn Asn Lys GlnGln Asn Asn Val Thr His 20 25 30 409 26 PRT Plasmodium falciparum 409Lys Lys Ile Glu Tyr Thr Asn Lys Ile Thr His Phe Phe Lys Ala Lys 1 5 1015 Asn Asn Lys Gln Gln Asn Asn Val Thr His 20 25 410 25 PRT Plasmodiumfalciparum 410 Lys Ile Glu Tyr Thr Asn Lys Ile Thr His Phe Phe Lys AlaLys Asn 1 5 10 15 Asn Lys Gln Gln Asn Asn Val Thr His 20 25 411 19 PRTPlasmodium falciparum 411 Lys Ile Thr His Phe Phe Lys Ala Lys Asn AsnLys Gln Gln Asn Asn 1 5 10 15 Val Thr His 412 48 PRT Plasmodiumfalciparum 412 His Lys Asn Asn Glu Asp Ile Lys Asn Asp Asn Ser Lys AspIle Lys 1 5 10 15 Asn Asp Asn Ser Lys Asp Ile Lys Asn Asp Asn Ser LysAsp Ile Lys 20 25 30 Asn Asp Asn Asn Glu Asp Ile Lys Asn Asp Asn Ser LysAsp Ile Lys 35 40 45 413 45 PRT Plasmodium falciparum 413 His Lys AsnAsn Glu Asp Ile Lys Asn Asp Asn Ser Lys Asp Ile Lys 1 5 10 15 Asn AspAsn Ser Lys Asp Ile Lys Asn Asp Asn Ser Lys Asp Ile Lys 20 25 30 Asn AspAsn Asn Glu Asp Ile Lys Asn Asp Asn Ser Lys 35 40 45 414 40 PRTPlasmodium falciparum 414 His Lys Asn Asn Glu Asp Ile Lys Asn Asp AsnSer Lys Asp Ile Lys 1 5 10 15 Asn Asp Asn Ser Lys Asp Ile Lys Asn AspAsn Ser Lys Asp Ile Lys 20 25 30 Asn Asp Asn Asn Glu Asp Ile Lys 35 40415 32 PRT Plasmodium falciparum 415 His Lys Asn Asn Glu Asp Ile Lys AsnAsp Asn Ser Lys Asp Ile Lys 1 5 10 15 Asn Asp Asn Ser Lys Asp Ile LysAsn Asp Asn Ser Lys Asp Ile Lys 20 25 30 416 29 PRT Plasmodiumfalciparum 416 His Lys Asn Asn Glu Asp Ile Lys Asn Asp Asn Ser Lys AspIle Lys 1 5 10 15 Asn Asp Asn Ser Lys Asp Ile Lys Asn Asp Asn Ser Lys 2025 417 24 PRT Plasmodium falciparum 417 His Lys Asn Asn Glu Asp Ile LysAsn Asp Asn Ser Lys Asp Ile Lys 1 5 10 15 Asn Asp Asn Ser Lys Asp IleLys 20 418 21 PRT Plasmodium falciparum 418 His Lys Asn Asn Glu Asp IleLys Asn Asp Asn Ser Lys Asp Ile Lys 1 5 10 15 Asn Asp Asn Ser Lys 20 41916 PRT Plasmodium falciparum 419 His Lys Asn Asn Glu Asp Ile Lys Asn AspAsn Ser Lys Asp Ile Lys 1 5 10 15 420 8 PRT Plasmodium falciparum 420His Lys Asn Asn Glu Asp Ile Lys 1 5 421 31 PRT Plasmodium falciparum 421Lys Lys Tyr Asp Asp Leu Gln Asn Lys Tyr Asn Ile Leu Asn Lys Leu 1 5 1015 Lys Asn Ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys Tyr His 20 25 30422 30 PRT Plasmodium falciparum 422 Lys Tyr Asp Asp Leu Gln Asn Lys TyrAsn Ile Leu Asn Lys Leu Lys 1 5 10 15 Asn Ser Leu Glu Glu Lys Asn GluGlu Leu Lys Lys Tyr His 20 25 30 423 23 PRT Plasmodium falciparum 423Lys Tyr Asn Ile Leu Asn Lys Leu Lys Asn Ser Leu Glu Glu Lys Asn 1 5 1015 Glu Glu Leu Lys Lys Tyr His 20 424 17 PRT Plasmodium falciparum 424Lys Leu Lys Asn Ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys Tyr 1 5 1015 His 425 15 PRT Plasmodium falciparum 425 Lys Asn Ser Leu Glu Glu LysAsn Glu Glu Leu Lys Lys Tyr His 1 5 10 15 426 9 PRT Plasmodiumfalciparum 426 Lys Asn Glu Glu Leu Lys Lys Tyr His 1 5 427 35 PRTPlasmodium falciparum 427 His Met Gly Asn Asn Gln Asp Ile Asn Glu AsnVal Tyr Asn Ile Lys 1 5 10 15 Pro Gln Glu Phe Lys Glu Glu Glu Glu GluAsp Ile Ser Met Val Asn 20 25 30 Thr Lys Lys 35 428 17 PRT Plasmodiumfalciparum 428 Lys Asn Ser Asn Glu Leu Lys Arg Ile Asn Asp Asn Phe PheLys Leu 1 5 10 15 His 429 55 PRT Plasmodium falciparum 429 Lys Pro CysLeu Tyr Lys Lys Cys Lys Ile Ser Gln Cys Leu Tyr Lys 1 5 10 15 Lys CysLys Ile Ser Gln Val Trp Trp Cys Met Pro Val Lys Asp Thr 20 25 30 Phe AsnThr Tyr Glu Arg Asn Asn Val Leu Asn Ser Lys Ile Glu Asn 35 40 45 Asn IleGlu Lys Ile Pro His 50 55 430 40 PRT Plasmodium falciparum 430 His IleAsn Asn Glu Tyr Thr Asn Lys Asn Pro Lys Asn Cys Leu Leu 1 5 10 15 TyrLys Asn Glu Glu Arg Asn Tyr Asn Asp Asn Asn Ile Lys Asp Tyr 20 25 30 IleAsn Ser Met Asn Phe Lys Lys 35 40 431 39 PRT Plasmodium falciparum 431His Ile Asn Asn Glu Tyr Thr Asn Lys Asn Pro Lys Asn Cys Leu Leu 1 5 1015 Tyr Lys Asn Glu Glu Arg Asn Tyr Asn Asp Asn Asn Ile Lys Asp Tyr 20 2530 Ile Asn Ser Met Asn Phe Lys 35 432 18 PRT Plasmodium falciparum 432His Ile Asn Asn Glu Tyr Thr Asn Lys Asn Pro Lys Asn Cys Leu Leu 1 5 1015 Tyr Lys 433 23 PRT Plasmodium falciparum 433 Lys Asn Lys Thr Asn GlnSer Lys Gly Val Lys Gly Glu Tyr Glu Lys 1 5 10 15 Lys Lys Glu Thr AsnGly His 20 434 21 PRT Plasmodium falciparum 434 Lys Thr Asn Gln Ser LysGly Val Lys Gly Glu Tyr Glu Lys Lys Lys 1 5 10 15 Glu Thr Asn Gly His 20435 16 PRT Plasmodium falciparum 435 Lys Gly Val Lys Gly Glu Tyr Glu LysLys Lys Glu Thr Asn Gly His 1 5 10 15 436 13 PRT Plasmodium falciparum436 Lys Gly Glu Tyr Glu Lys Lys Lys Glu Thr Asn Gly His 1 5 10 437 28PRT Plasmodium falciparum 437 Lys Ser Gly Met Tyr Thr Asn Glu Gly AsnLys Ser Cys Glu Cys Ser 1 5 10 15 Tyr Lys Lys Lys Ser Ser Ser Ser AsnLys Val His 20 25 438 18 PRT Plasmodium falciparum 438 Lys Ser Cys GluCys Ser Tyr Lys Lys Lys Ser Ser Ser Ser Asn Lys 1 5 10 15 Val His 439 11PRT Plasmodium falciparum 439 Lys Lys Lys Ser Ser Ser Ser Asn Lys ValHis 1 5 10 440 10 PRT Plasmodium falciparum 440 Lys Lys Ser Ser Ser SerAsn Lys Val His 1 5 10 441 9 PRT Plasmodium falciparum 441 Lys Ser SerSer Ser Asn Lys Val His 1 5 442 30 PRT Plasmodium falciparum 442 His IleMet Leu Lys Ser Gly Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 10 15 CysGlu Cys Ser Tyr Lys Lys Lys Ser Ser Ser Ser Asn Lys 20 25 30 443 24 PRTPlasmodium falciparum 443 His Ile Met Leu Lys Ser Gly Met Tyr Thr AsnGlu Gly Asn Lys Ser 1 5 10 15 Cys Glu Cys Ser Tyr Lys Lys Lys 20 444 23PRT Plasmodium falciparum 444 His Ile Met Leu Lys Ser Gly Met Tyr ThrAsn Glu Gly Asn Lys Ser 1 5 10 15 Cys Glu Cys Ser Tyr Lys Lys 20 445 22PRT Plasmodium falciparum 445 His Ile Met Leu Lys Ser Gly Met Tyr ThrAsn Glu Gly Asn Lys Ser 1 5 10 15 Cys Glu Cys Ser Tyr Lys 20 446 50 PRTPlasmodium falciparum 446 Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu LysThr Gln Ile Asn Lys 1 5 10 15 Thr Lys Tyr Glu Arg Gly Asp Val Ile IleAsp Asn Thr Glu Ile Gln 20 25 30 Lys Ile Ile Ile Arg Asp Tyr His Glu ThrLeu Asn Val His Lys Leu 35 40 45 Asp His 50 447 43 PRT Plasmodiumfalciparum 447 Lys Arg Glu Lys Thr Gln Ile Asn Lys Thr Lys Tyr Glu ArgGly Asp 1 5 10 15 Val Ile Ile Asp Asn Thr Glu Ile Gln Lys Ile Ile IleArg Asp Tyr 20 25 30 His Glu Thr Leu Asn Val His Lys Leu Asp His 35 40448 40 PRT Plasmodium falciparum 448 Lys Thr Gln Ile Asn Lys Thr Lys TyrGlu Arg Gly Asp Val Ile Ile 1 5 10 15 Asp Asn Thr Glu Ile Gln Lys IleIle Ile Arg Asp Tyr His Glu Thr 20 25 30 Leu Asn Val His Lys Leu Asp His35 40 449 46 PRT Plasmodium falciparum 449 Lys Pro Leu Ala Lys Leu ArgLys Arg Glu Lys Thr Gln Ile Asn Lys 1 5 10 15 Thr Lys Tyr Glu Arg GlyAsp Val Ile Ile Asp Asn Thr Glu Ile Gln 20 25 30 Lys Ile Ile Ile Arg AspTyr His Glu Thr Leu Asn Val His 35 40 45 450 40 PRT Plasmodiumfalciparum 450 Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu Lys Thr Gln IleAsn Lys 1 5 10 15 Thr Lys Tyr Glu Arg Gly Asp Val Ile Ile Asp Asn ThrGlu Ile Gln 20 25 30 Lys Ile Ile Ile Arg Asp Tyr His 35 40 451 36 PRTPlasmodium falciparum 451 Lys Leu Arg Lys Arg Glu Lys Thr Gln Ile AsnLys Thr Lys Tyr Glu 1 5 10 15 Arg Gly Asp Val Ile Ile Asp Asn Thr GluIle Gln Lys Ile Ile Ile 20 25 30 Arg Asp Tyr His 35 452 33 PRTPlasmodium falciparum 452 Lys Arg Glu Lys Thr Gln Ile Asn Lys Thr LysTyr Glu Arg Gly Asp 1 5 10 15 Val Ile Ile Asp Asn Thr Glu Ile Gln LysIle Ile Ile Arg Asp Tyr 20 25 30 His 453 30 PRT Plasmodium falciparum453 Lys Thr Gln Ile Asn Lys Thr Lys Tyr Glu Arg Gly Asp Val Ile Ile 1 510 15 Asp Asn Thr Glu Ile Gln Lys Ile Ile Ile Arg Asp Tyr His 20 25 30454 41 PRT Plasmodium falciparum 454 Lys Lys Asp Lys Glu Lys Lys Lys AspSer Asn Glu Asn Arg Lys Lys 1 5 10 15 Lys Gln Lys Glu Asp Lys Lys AsnPro Asn Asp Asn Lys Leu Lys Lys 20 25 30 Ile Glu Tyr Thr Asn Lys Ile ThrHis 35 40 455 40 PRT Plasmodium falciparum 455 Lys Asp Lys Glu Lys LysLys Asp Ser Asn Glu Asn Arg Lys Lys Lys 1 5 10 15 Gln Lys Glu Asp LysLys Asn Pro Asn Asp Asn Lys Leu Lys Lys Ile 20 25 30 Glu Tyr Thr Asn LysIle Thr His 35 40 456 38 PRT Plasmodium falciparum 456 Lys Glu Lys LysLys Asp Ser Asn Glu Asn Arg Lys Lys Lys Gln Lys 1 5 10 15 Glu Asp LysLys Asn Pro Asn Asp Asn Lys Leu Lys Lys Ile Glu Tyr 20 25 30 Thr Asn LysIle Thr His 35 457 36 PRT Plasmodium falciparum 457 Lys Lys Lys Asp SerAsn Glu Asn Arg Lys Lys Lys Gln Lys Glu Asp 1 5 10 15 Lys Lys Asn ProAsn Asp Asn Lys Leu Lys Lys Ile Glu Tyr Thr Asn 20 25 30 Lys Ile Thr His35 458 35 PRT Plasmodium falciparum 458 Lys Lys Asp Ser Asn Glu Asn ArgLys Lys Lys Gln Lys Glu Asp Lys 1 5 10 15 Lys Asn Pro Asn Asp Asn LysLeu Lys Lys Ile Glu Tyr Thr Asn Lys 20 25 30 Ile Thr His 35 459 34 PRTPlasmodium falciparum 459 Lys Asp Ser Asn Glu Asn Arg Lys Lys Lys GlnLys Glu Asp Lys Lys 1 5 10 15 Asn Pro Asn Asp Asn Lys Leu Lys Lys IleGlu Tyr Thr Asn Lys Ile 20 25 30 Thr His 460 27 PRT Plasmodiumfalciparum 460 Lys Lys Lys Gln Lys Glu Asp Lys Lys Asn Pro Asn Asp AsnLys Leu 1 5 10 15 Lys Lys Ile Glu Tyr Thr Asn Lys Ile Thr His 20 25 46126 PRT Plasmodium falciparum 461 Lys Lys Gln Lys Glu Asp Lys Lys Asn ProAsn Asp Asn Lys Leu Lys 1 5 10 15 Lys Ile Glu Tyr Thr Asn Lys Ile ThrHis 20 25 462 25 PRT Plasmodium falciparum 462 Lys Gln Lys Glu Asp LysLys Asn Pro Asn Asp Asn Lys Leu Lys Lys 1 5 10 15 Ile Glu Tyr Thr AsnLys Ile Thr His 20 25 463 23 PRT Plasmodium falciparum 463 Lys Glu AspLys Lys Asn Pro Asn Asp Asn Lys Leu Lys Lys Ile Glu 1 5 10 15 Tyr ThrAsn Lys Ile Thr His 20 464 20 PRT Plasmodium falciparum 464 Lys Lys AsnPro Asn Asp Asn Lys Leu Lys Lys Ile Glu Tyr Thr Asn 1 5 10 15 Lys IleThr His 20 465 19 PRT Plasmodium falciparum 465 Lys Asn Pro Asn Asp AsnLys Leu Lys Lys Ile Glu Tyr Thr Asn Lys 1 5 10 15 Ile Thr His 466 13 PRTPlasmodium falciparum 466 Lys Leu Lys Lys Ile Glu Tyr Thr Asn Lys IleThr His 1 5 10 467 11 PRT Plasmodium falciparum 467 Lys Lys Ile Glu TyrThr Asn Lys Ile Thr His 1 5 10 468 10 PRT Plasmodium falciparum 468 LysIle Glu Tyr Thr Asn Lys Ile Thr His 1 5 10 469 44 PRT Plasmodiumfalciparum 469 His Gly Gln Ile Lys Ile Glu Asp Val Asn Asn Glu Asn PheAsn Asn 1 5 10 15 Glu Gln Met Lys Asn Lys Tyr Asn Asp Glu Glu Lys MetAsp Ile Ser 20 25 30 Lys Ser Lys Ser Leu Lys Ser Asp Phe Leu Glu Lys 3540 470 38 PRT Plasmodium falciparum 470 His Gly Gln Ile Lys Ile Glu AspVal Asn Asn Glu Asn Phe Asn Asn 1 5 10 15 Glu Gln Met Lys Asn Lys TyrAsn Asp Glu Glu Lys Met Asp Ile Ser 20 25 30 Lys Ser Lys Ser Leu Lys 35471 35 PRT Plasmodium falciparum 471 His Gly Gln Ile Lys Ile Glu Asp ValAsn Asn Glu Asn Phe Asn Asn 1 5 10 15 Glu Gln Met Lys Asn Lys Tyr AsnAsp Glu Glu Lys Met Asp Ile Ser 20 25 30 Lys Ser Lys 35 472 33 PRTPlasmodium falciparum 472 His Gly Gln Ile Lys Ile Glu Asp Val Asn AsnGlu Asn Phe Asn Asn 1 5 10 15 Glu Gln Met Lys Asn Lys Tyr Asn Asp GluGlu Lys Met Asp Ile Ser 20 25 30 Lys 473 31 PRT Plasmodium falciparum473 Lys Lys Tyr Asp Asp Leu Gln Asn Lys Tyr Asn Ile Leu Asn Lys Leu 1 510 15 Lys Asn Ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys Tyr His 20 2530 474 30 PRT Plasmodium falciparum 474 Lys Tyr Asp Asp Leu Gln Asn LysTyr Asn Ile Leu Asn Lys Leu Lys 1 5 10 15 Asn Ser Leu Glu Glu Lys AsnGlu Glu Leu Lys Lys Tyr His 20 25 30 475 23 PRT Plasmodium falciparum475 Lys Tyr Asn Ile Leu Asn Lys Leu Lys Asn Ser Leu Glu Glu Lys Asn 1 510 15 Glu Glu Leu Lys Lys Tyr His 20 476 17 PRT Plasmodium falciparum476 Lys Leu Lys Asn Ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys Tyr 1 510 15 His 477 15 PRT Plasmodium falciparum 477 Lys Asn Ser Leu Glu GluLys Asn Glu Glu Leu Lys Lys Tyr His 1 5 10 15 478 9 PRT Plasmodiumfalciparum 478 Lys Asn Glu Glu Leu Lys Lys Tyr His 1 5 479 44 PRTPlasmodium falciparum 479 His Met Gly Asn Asn Gln Asp Ile Asn Glu AsnVal Tyr Asn Ile Lys 1 5 10 15 Pro Gln Glu Phe Lys Glu Glu Glu Glu GluAsp Ile Ser Met Val Asn 20 25 30 Thr Lys Lys Cys Asp Asp Ile Gln Glu AsnIle Lys 35 40 480 50 PRT Plasmodium falciparum 480 Lys Thr Asn Leu TyrAsn Ile Tyr Asn Asn Lys Asn Asp Asp Lys Asp 1 5 10 15 Asn Ile Leu AspAsn Glu Asn Arg Glu Gly Leu Tyr Leu Cys Asp Val 20 25 30 Met Lys Asn SerAsn Glu Leu Lys Arg Ile Asn Asp Asn Phe Phe Lys 35 40 45 Leu His 50 48117 PRT Plasmodium falciparum 481 Lys Asn Ser Asn Glu Leu Lys Arg Ile AsnAsp Asn Phe Phe Lys Leu 1 5 10 15 His 482 11 PRT Plasmodium falciparum482 Lys Arg Ile Asn Asp Asn Phe Phe Lys Leu His 1 5 10 483 40 PRTPlasmodium falciparum 483 His Ile Asn Asn Glu Tyr Thr Asn Lys Asn ProLys Asn Cys Leu Leu 1 5 10 15 Tyr Lys Asn Glu Glu Arg Asn Tyr Asn AspAsn Asn Ile Lys Asp Tyr 20 25 30 Ile Asn Ser Met Asn Phe Lys Lys 35 40484 39 PRT Plasmodium falciparum 484 His Ile Asn Asn Glu Tyr Thr Asn LysAsn Pro Lys Asn Cys Leu Leu 1 5 10 15 Tyr Lys Asn Glu Glu Arg Asn TyrAsn Asp Asn Asn Ile Lys Asp Tyr 20 25 30 Ile Asn Ser Met Asn Phe Lys 35485 18 PRT Plasmodium falciparum 485 His Ile Asn Asn Glu Tyr Thr Asn LysAsn Pro Lys Asn Cys Leu Leu 1 5 10 15 Tyr Lys 486 45 PRT Plasmodiumfalciparum 486 Lys Pro Cys Leu Tyr Lys Lys Cys Lys Ile Ser Gln Val TrpTrp Cys 1 5 10 15 Met Pro Val Lys Asp Thr Phe Asn Thr Tyr Glu Arg AsnAsn Val Leu 20 25 30 Asn Ser Lys Ile Glu Asn Asn Ile Glu Lys Ile Pro His35 40 45 487 39 PRT Plasmodium falciparum 487 Lys Cys Lys Ile Ser GlnVal Trp Trp Cys Met Pro Val Lys Asp Thr 1 5 10 15 Phe Asn Thr Tyr GluArg Asn Asn Val Leu Asn Ser Lys Ile Glu Asn 20 25 30 Asn Ile Glu Lys IlePro His 35 488 11 PRT Plasmodium falciparum 488 Lys Ile Glu Asn Asn IleGlu Lys Ile Pro His 1 5 10 489 23 PRT Plasmodium falciparum 489 Lys AsnLys Thr Asn Gly Ser Lys Gly Val Lys Gly Glu Tyr Glu Lys 1 5 10 15 LysLys Glu Thr Asn Gly His 20 490 21 PRT Plasmodium falciparum 490 Lys ThrAsn Gly Ser Lys Gly Val Lys Gly Glu Tyr Glu Lys Lys Lys 1 5 10 15 GluThr Asn Gly His 20 491 16 PRT Plasmodium falciparum 491 Lys Gly Val LysGly Glu Tyr Glu Lys Lys Lys Glu Thr Asn Gly His 1 5 10 15 492 13 PRTPlasmodium falciparum 492 Lys Gly Glu Tyr Glu Lys Lys Lys Glu Thr AsnGly His 1 5 10 493 60 PRT Plasmodium falciparum 493 Lys Thr Ile Glu LysIle Asn Lys Ser Lys Ser Trp Phe Phe Glu Glu 1 5 10 15 Leu Asp Glu IleAsp Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu Lys 20 25 30 Thr Gln Ile AsnLys Thr Lys Tyr Glu Arg Gly Asp Val Ile Ile Asp 35 40 45 Asn Thr Glu IleGln Lys Ile Ile Arg Asp Tyr His 50 55 60 494 56 PRT Plasmodiumfalciparum 494 Lys Ile Asn Lys Ser Lys Ser Trp Phe Phe Glu Glu Leu AspGlu Ile 1 5 10 15 Asp Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu Lys ThrGln Ile Asn 20 25 30 Lys Thr Lys Tyr Glu Arg Gly Asp Val Ile Ile Asp AsnThr Glu Ile 35 40 45 Gln Lys Ile Ile Arg Asp Tyr His 50 55 495 39 PRTPlasmodium falciparum 495 Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu LysThr Gln Ile Asn Lys 1 5 10 15 Thr Lys Tyr Glu Arg Gly Asp Val Ile IleAsp Asn Thr Glu Ile Gln 20 25 30 Lys Ile Ile Arg Asp Tyr His 35 496 32PRT Plasmodium falciparum 496 His Ile Met Leu Lys Ser Gln Met Tyr ThrAsn Glu Gly Asn Lys Ser 1 5 10 15 Cys Glu Cys Ser Tyr Lys Lys Lys SerSer Ser Ser Asn Lys Val His 20 25 30 497 35 PRT Plasmodium falciparum497 Lys Leu Arg Lys Arg Glu Lys Thr Gln Ile Asn Lys Thr Lys Tyr Glu 1 510 15 Arg Gly Asp Val Ile Ile Asp Asn Thr Glu Ile Gln Lys Ile Ile Arg 2025 30 Asp Tyr His 35 498 32 PRT Plasmodium falciparum 498 Lys Arg GluLys Thr Gln Ile Asn Lys Thr Lys Tyr Glu Arg Gly Asp 1 5 10 15 Val IleIle Asp Asn Thr Glu Ile Gln Lys Ile Ile Arg Asp Tyr His 20 25 30 499 29PRT Plasmodium falciparum 499 Lys Thr Gln Ile Asn Lys Thr Lys Tyr GluArg Gly Asp Val Ile Ile 1 5 10 15 Asp Asn Thr Glu Ile Gln Lys Ile IleArg Asp Tyr His 20 25 500 48 PRT Plasmodium falciparum 500 Lys Pro LeuAla Lys Leu Arg Lys Arg Glu Lys Thr Gln Ile Asn Lys 1 5 10 15 Thr LysTyr Glu Arg Gly Asp Val Ile Ile Asp Asn Thr Glu Ile Gln 20 25 30 Lys IleIle Arg Asp Tyr His Thr Leu Asn Val His Lys Leu Asp His 35 40 45 501 44PRT Plasmodium falciparum 501 Lys Leu Arg Lys Arg Glu Lys Thr Gln IleAsn Lys Thr Lys Tyr Glu 1 5 10 15 Arg Gly Asp Val Ile Ile Asp Asn ThrGlu Ile Gln Lys Ile Ile Arg 20 25 30 Asp Tyr His Thr Leu Asn Val His LysLeu Asp His 35 40 502 41 PRT Plasmodium falciparum 502 Lys Arg Glu LysThr Gln Ile Asn Lys Thr Lys Tyr Glu Arg Gly Asp 1 5 10 15 Val Ile IleAsp Asn Thr Glu Ile Gln Lys Ile Ile Arg Asp Tyr His 20 25 30 Thr Leu AsnVal His Lys Leu Asp His 35 40 503 38 PRT Plasmodium falciparum 503 LysThr Gln Ile Asn Lys Thr Lys Tyr Glu Arg Gly Asp Val Ile Ile 1 5 10 15Asp Asn Thr Glu Ile Gln Lys Ile Ile Arg Asp Tyr His Thr Leu Asn 20 25 30Val His Lys Leu Asp His 35 504 44 PRT Plasmodium falciparum 504 Lys ProLeu Ala Lys Leu Arg Lys Arg Glu Lys Thr Gln Ile Asn Lys 1 5 10 15 ThrLys Tyr Glu Arg Gly Asp Val Ile Ile Asp Asn Thr Glu Ile Gln 20 25 30 LysIle Ile Arg Asp Tyr His Thr Leu Asn Val His 35 40 505 40 PRT Plasmodiumfalciparum 505 Lys Leu Arg Lys Arg Glu Lys Thr Gln Ile Asn Lys Thr LysTyr Glu 1 5 10 15 Arg Gly Asp Val Ile Ile Asp Asn Thr Glu Ile Gln LysIle Ile Arg 20 25 30 Asp Tyr His Thr Leu Asn Val His 35 40 506 37 PRTPlasmodium falciparum 506 Lys Arg Glu Lys Thr Gln Ile Asn Lys Thr LysTyr Glu Arg Gly Asp 1 5 10 15 Val Ile Ile Asp Asn Thr Glu Ile Gln LysIle Ile Arg Asp Tyr His 20 25 30 Thr Leu Asn Val His 35 507 34 PRTPlasmodium falciparum 507 Lys Thr Gln Ile Asn Lys Thr Lys Tyr Glu ArgGly Asp Val Ile Ile 1 5 10 15 Asp Asn Thr Glu Ile Gln Lys Ile Ile ArgAsp Tyr His Thr Leu Asn 20 25 30 Val His 508 32 PRT Plasmodiumfalciparum 508 His Ile Met Leu Lys Ser Gln Met Tyr Thr Asn Glu Gly AsnLys Ser 1 5 10 15 Cys Glu Cys Ser Tyr Lys Lys Lys Ser Ser Ser Ser AsnLys Val His 20 25 30 509 28 PRT Plasmodium falciparum 509 Lys Ser GlnMet Tyr Thr Asn Glu Gly Asn Lys Ser Cys Glu Cys Ser 1 5 10 15 Tyr LysLys Lys Ser Ser Ser Ser Asn Lys Val His 20 25 510 18 PRT Plasmodiumfalciparum 510 Lys Ser Cys Glu Cys Ser Tyr Lys Lys Lys Ser Ser Ser SerAsn Lys 1 5 10 15 Val His 511 11 PRT Plasmodium falciparum 511 Lys LysLys Ser Ser Ser Ser Asn Lys Val His 1 5 10 512 10 PRT Plasmodiumfalciparum 512 Lys Lys Ser Ser Ser Ser Asn Lys Val His 1 5 10 513 9 PRTPlasmodium falciparum 513 Lys Ser Ser Ser Ser Asn Lys Val His 1 5 514 30PRT Plasmodium falciparum 514 His Ile Met Leu Lys Ser Gln Met Tyr ThrAsn Glu Gly Asn Lys Ser 1 5 10 15 Cys Glu Cys Ser Tyr Lys Lys Lys SerSer Ser Ser Asn Lys 20 25 30 515 24 PRT Plasmodium falciparum 515 HisIle Met Leu Lys Ser Gln Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 10 15Cys Glu Cys Ser Tyr Lys Lys Lys 20 516 23 PRT Plasmodium falciparum 516His Ile Met Leu Lys Ser Gln Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 1015 Cys Glu Cys Ser Tyr Lys Lys 20 517 22 PRT Plasmodium falciparum 517His Ile Met Leu Lys Ser Gln Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 1015 Cys Glu Cys Ser Tyr Lys 20 518 36 PRT Plasmodium falciparum 518 HisAsn Asn His Asn Ile Gln Ile Tyr Lys Asp Lys Arg Ile Asn Phe 1 5 10 15Met Asn Pro His Lys Val Met Tyr His Asp Asn Met Ser Lys Asn Glu 20 25 30Arg Thr Glu Lys 35 519 30 PRT Plasmodium falciparum 519 His Asn Asn HisAsn Ile Gln Ile Tyr Lys Asp Lys Arg Ile Asn Phe 1 5 10 15 Met Asn ProHis Lys Val Met Tyr His Asp Asn Met Ser Lys 20 25 30 520 21 PRTPlasmodium falciparum 520 His Asn Asn His Asn Ile Gln Ile Tyr Lys AspLys Arg Ile Asn Phe 1 5 10 15 Met Asn Pro His Lys 20 521 17 PRTPlasmodium falciparum 521 His Lys Val Met Tyr His Asp Asn Met Ser LysAsn Glu Arg Thr Glu 1 5 10 15 Lys 522 11 PRT Plasmodium falciparum 522His Lys Val Met Tyr His Asp Asn Met Ser Lys 1 5 10 523 40 PRT Homosapiens 523 His Arg Glu Ile Cys Thr Ile Gln Ser Ser Gly Gly Ile Met LeuLeu 1 5 10 15 Lys Asp Gln Val Leu Arg Cys Ser Lys Ile Ala Gly Val LysVal Ala 20 25 30 Glu Ile Thr Glu Leu Ile Leu Lys 35 40 524 25 PRT Homosapiens 524 His Arg Glu Ile Cys Thr Ile Gln Ser Ser Gly Gly Ile Met LeuLeu 1 5 10 15 Lys Asp Gln Val Leu Arg Cys Ser Lys 20 25 525 47 PRT Homosapiens 525 His Arg Glu Ile Cys Thr Ile Gln Ser Ser Gly Gly Ile Met LeuLeu 1 5 10 15 Lys Asp Gln Val Leu Arg Cys Ser Lys Ile Ala Gly Val LysVal Ala 20 25 30 Glu Ile Thr Glu Leu Ile Leu Lys Ala Leu Glu Asn Asp GlnLys 35 40 45 526 40 PRT Homo sapiens 526 His Arg Glu Ile Cys Thr Ile GlnAla Ala Gly Gly Ile Met Leu Leu 1 5 10 15 Lys Asp Gln Val Leu Arg CysSer Lys Ile Ala Gly Val Lys Val Ala 20 25 30 Glu Ile Thr Glu Leu Ile LeuLys 35 40 527 23 PRT Homo sapiens 527 Lys Lys Met Gln Gln Glu Asn MetLys Pro Gln Glu Gln Leu Thr Leu 1 5 10 15 Glu Pro Tyr Glu Arg Asp His 20528 22 PRT Homo sapiens 528 Lys Met Gln Gln Glu Asn Met Lys Pro Gln GluGln Leu Thr Leu Glu 1 5 10 15 Pro Tyr Glu Arg Asp His 20 529 38 PRT Homosapiens 529 His Glu Met Glu Glu Ser Lys Lys Asn Arg Val Glu Ile Asn AspVal 1 5 10 15 Glu Pro Glu Val Phe Lys Glu Met Met Cys Phe Ile Tyr ThrGly Lys 20 25 30 Ala Pro Asn Leu Asp Lys 35 530 32 PRT Homo sapiens 530His Glu Met Glu Glu Ser Lys Lys Asn Arg Val Glu Ile Asn Asp Val 1 5 1015 Glu Pro Glu Val Phe Lys Glu Met Met Cys Phe Ile Tyr Thr Gly Lys 20 2530 531 9 PRT Homo sapiens 531 Lys His Gly Glu Leu Lys Val Tyr Lys 1 5532 14 PRT Homo sapiens 532 Lys Leu Ile Leu Gly Pro Gln Glu Glu Lys GlyLys Gln His 1 5 10 533 7 PRT Homo sapiens 533 Lys Asn Arg Ile His HisLys 1 5 534 17 PRT Homo sapiens 534 His His Asn Ser Ser Arg Lys Ser ThrLys Lys Thr Asn Gln Ser Ser 1 5 10 15 Lys 535 16 PRT Homo sapiens 535His Asn Ser Ser Arg Lys Ser Thr Lys Lys Thr Asn Gln Ser Ser Lys 1 5 1015 536 20 PRT Homo sapiens 536 Lys His His Asn Ile Leu Pro Lys Thr LeuAla Asn Asp Lys His Ser 1 5 10 15 His Lys Pro His 20 537 17 PRT Homosapiens 537 His His Asn Ile Leu Pro Lys Thr Leu Ala Asn Asp Lys His SerHis 1 5 10 15 Lys 538 16 PRT Homo sapiens 538 His Asn Ile Leu Pro LysThr Leu Ala Asn Asp Lys His Ser His Lys 1 5 10 15 539 12 PRT Homosapiens 539 His Asn Ile Leu Pro Lys Thr Leu Ala Asn Asp Lys 1 5 10 54018 PRT Homo sapiens 540 Lys Asn Thr Pro Asp Ser Lys Lys Ile Ser Ser ArgAsn Ile Asn Asp 1 5 10 15 His His 541 17 PRT Homo sapiens 541 Lys AsnThr Pro Asp Ser Lys Lys Ile Ser Ser Arg Asn Ile Asn Asp 1 5 10 15 His542 27 PRT Homo sapiens 542 Lys Asp Thr Cys Ile Gln Ser Pro Ser Lys GluCys Gln Lys Ser His 1 5 10 15 Pro Lys Ser Val Pro Val Ser Ser Lys LysLys 20 25 543 26 PRT Homo sapiens 543 Lys Asp Thr Cys Ile Gln Ser ProSer Lys Glu Cys Gln Lys Ser His 1 5 10 15 Pro Lys Ser Val Pro Val SerSer Lys Lys 20 25 544 12 PRT Homo sapiens 544 His Pro Lys Ser Val ProVal Ser Ser Lys Lys Lys 1 5 10 545 11 PRT Homo sapiens 545 His Pro LysSer Val Pro Val Ser Ser Lys Lys 1 5 10 546 10 PRT Homo sapiens 546 HisPro Lys Ser Val Pro Val Ser Ser Lys 1 5 10 547 14 PRT Homo sapiens 547Lys Ala Leu Gln Glu Lys Val Glu Ile Lys Gln Leu Asn His 1 5 10 548 42PRT Homo sapiens 548 Lys Thr Leu Phe Pro Leu Ile Glu Ala Lys Lys Lys AspGln Val Thr 1 5 10 15 Ala Gln Glu Ile Phe Gln Asp Asn His Glu Asp GlyPro Thr Ala Lys 20 25 30 Lys Leu Lys Thr Glu Gln Gly Gly Ala His 35 40549 25 PRT Homo sapiens 549 Lys Thr Leu Phe Pro Leu Ile Glu Ala Lys LysLys Asp Gln Val Thr 1 5 10 15 Ala Gln Glu Ile Phe Gln Asp Asn His 20 25550 14 PRT Homo sapiens 550 Lys Leu Cys Val Phe Lys Lys Ile Glu Arg HisSer Ile His 1 5 10 551 11 PRT Homo sapiens 551 Lys Leu Cys Val Phe LysLys Ile Glu Arg His 1 5 10 552 22 PRT Homo sapiens 552 His Gly Pro SerPhe Pro Leu Lys Gly Ile Thr Glu Gln Gln Lys Glu 1 5 10 15 Gly Leu GluIle Val Lys 20 553 15 PRT Homo sapiens 553 His Gly Pro Ser Phe Pro LeuLys Gly Ile Thr Glu Gln Gln Lys 1 5 10 15 554 13 PRT Homo sapiens 554His Thr Leu Leu Lys Ile Leu Ser Thr Phe Leu Phe Lys 1 5 10 555 14 PRTHomo sapiens 555 His Leu Leu Gly Asn Asn Asp Lys Asn Leu Leu Pro Ser Lys1 5 10 556 19 PRT Homo sapiens 556 His Arg His Glu Gly Val Phe Ile CysArg Gly Lys Glu Asp Ala Leu 1 5 10 15 Val Thr Lys 557 17 PRT Homosapiens 557 His Glu Gly Val Phe Ile Cys Arg Gly Lys Glu Asp Ala Leu ValThr 1 5 10 15 Lys 558 20 PRT Homo sapiens 558 His Ser Gly Gly Asn ArgGly Arg Gly Arg Gly Gly Lys Arg Gly Asn 1 5 10 15 Gln Ser Gly Lys 20 55915 PRT Homo sapiens 559 Lys Arg Gly Asn Gln Ser Gly Lys Asn Val Met ValGlu Pro His 1 5 10 15 560 17 PRT Homo sapiens 560 Lys Arg Gly Asn GlnSer Gly Lys Asn Val Met Val Glu Pro His Arg 1 5 10 15 His 561 23 PRTHomo sapiens 561 Lys Lys Met Gln Gln Glu Asn Met Lys Pro Gln Glu Gln LeuThr Leu 1 5 10 15 Glu Pro Tyr Glu Arg Asp His 20 562 22 PRT Homo sapiens562 Lys Met Gln Gln Glu Asn Met Lys Pro Gln Glu Gln Leu Thr Leu Glu 1 510 15 Pro Tyr Glu Arg Asp His 20 563 16 PRT Homo sapiens 563 His Ala TyrPro Glu Asp Ala Glu Asn Lys Glu Lys Glu Thr Ala Lys 1 5 10 15 564 22 PRTHomo sapiens 564 Lys Glu Ala Asn Val Lys Cys Pro Gln Ile Val Ile Ala PheTyr Glu 1 5 10 15 Glu Arg Leu Thr Trp His 20 565 25 PRT Homo sapiens 565Lys Val Leu Asp Arg Arg Val Val Lys Gly Gln Val Glu Tyr Leu Leu 1 5 1015 Lys Trp Lys Gly Phe Ser Glu Glu His 20 25 566 17 PRT Homo sapiens 566Lys Gly Gln Val Glu Tyr Leu Leu Lys Trp Lys Gly Phe Ser Glu Glu 1 5 1015 His 567 32 PRT Homo sapiens 567 Lys Ser Glu Val Ala Ala Gly Val LysLys Ser Gly Pro Leu Pro Ser 1 5 10 15 Ala Glu Arg Leu Glu Asn Val LeuPhe Gly Pro His Asp Cys Ser His 20 25 30 568 28 PRT Homo sapiens 568 LysSer Glu Val Ala Ala Gly Val Lys Lys Ser Gly Pro Leu Pro Ser 1 5 10 15Ala Glu Arg Leu Glu Asn Val Leu Phe Gly Pro His 20 25 569 28 PRT Homosapiens 569 Lys Ala Ala Glu Tyr Gly Lys Lys Ala Lys Ser Glu Thr Phe ArgLeu 1 5 10 15 Leu His Ala Lys Asn Ile Ile Arg Pro Gln Leu Lys 20 25 57020 PRT Homo sapiens 570 Lys Ala Ala Glu Tyr Gly Lys Lys Ala Lys Ser GluThr Phe Arg Leu 1 5 10 15 Leu His Ala Lys 20 571 11 PRT Homo sapiens 571Lys Ser Glu Thr Phe Arg Leu Leu His Ala Lys 1 5 10 572 11 PRT Homosapiens 572 His Ala Lys Asn Ile Ile Arg Pro Gln Leu Lys 1 5 10 573 12PRT Homo sapiens 573 His Met Met Leu Lys Ile Ala Glu Glu Leu Pro Lys 1 510 574 17 PRT Homo sapiens 574 His Ser Leu Asp His Leu Leu Lys Leu TyrCys Asn Val Asp Ser Asn 1 5 10 15 Lys 575 13 PRT Homo sapiens 575 HisLeu Leu Lys Leu Tyr Cys Asn Val Asp Ser Asn Lys 1 5 10 576 10 PRT Homosapiens 576 Lys Ala Lys Glu Arg Leu Glu Ala Lys His 1 5 10 577 8 PRTHomo sapiens 577 Lys Asp Arg Gln His Thr Leu Lys 1 5 578 9 PRT Homosapiens 578 Lys Asp Arg Gln His Thr Leu Lys His 1 5 579 12 PRT Homosapiens 579 Lys Glu Thr Cys Ser Glu Lys Ser Thr Asn Leu His 1 5 10 58016 PRT Homo sapiens 580 Lys Thr Glu Glu Ile Ser Glu Val Lys Met Asp AlaGlu Phe Gly His 1 5 10 15 581 24 PRT Homo sapiens 581 Lys Thr Glu GluIle Ser Glu Val Lys Met Asp Ala Glu Phe Gly His 1 5 10 15 Asp Ser GlyPhe Glu Val Arg His 20 582 17 PRT Homo sapiens 582 Lys Lys Tyr Val ArgAla Glu Gln Lys Asp Arg Gln His Thr Leu Lys 1 5 10 15 His 583 16 PRTHomo sapiens 583 Lys Tyr Val Arg Ala Glu Gln Lys Asp Arg Gln His Thr LeuLys His 1 5 10 15 584 13 PRT Homo sapiens 584 Lys Lys Tyr Val Arg AlaGlu Gln Lys Asp Arg Gln His 1 5 10 585 13 PRT Homo sapiens 585 Lys TyrVal Arg Ala Glu Gln Lys Asp Arg Gln His Thr 1 5 10 586 16 PRT Homosapiens 586 His His Val Phe Asn Met Leu Lys Lys Tyr Val Arg Ala Glu GlnLys 1 5 10 15 587 15 PRT Homo sapiens 587 His Val Phe Asn Met Leu LysLys Tyr Val Arg Ala Glu Gln Lys 1 5 10 15 588 24 PRT Homo sapiens 588His His Val Phe Asn Met Leu Lys Lys Tyr Val Arg Ala Glu Gln Lys 1 5 1015 Asp Arg Gln His Thr Leu Lys His 20 589 23 PRT Homo sapiens 589 HisVal Phe Asn Met Leu Lys Lys Tyr Val Arg Ala Glu Gln Lys Asp 1 5 10 15Arg Gln His Thr Leu Lys His 20 590 15 PRT Homo sapiens 590 His Ala HisPhe Gln Lys Ala Lys Glu Arg Leu Glu Ala Lys His 1 5 10 15 591 14 PRTHomo sapiens 591 His Ala His Phe Gln Lys Ala Lys Glu Arg Leu Glu Ala Lys1 5 10 592 12 PRT Homo sapiens 592 His Phe Gln Lys Ala Lys Glu Arg LeuGlu Ala Lys 1 5 10 593 30 PRT Homo sapiens 593 His Gln Glu Arg Met AspVal Cys Glu Thr His Leu His Trp His Thr 1 5 10 15 Val Ala Lys Glu ThrCys Ser Glu Lys Ser Thr Asn Leu His 20 25 30 594 25 PRT Homo sapiens 594His Gln Glu Arg Met Asp Val Cys Glu Thr His Leu His Trp His Thr 1 5 1015 Val Ala Lys Glu Thr Cys Ser Glu Lys 20 25 595 13 PRT Homo sapiens 595His Trp His Thr Val Ala Lys Glu Thr Cys Ser Glu Lys 1 5 10 596 11 PRTHomo sapiens 596 His Thr Val Ala Lys Glu Thr Cys Ser Glu Lys 1 5 10 59715 PRT Homo sapiens 597 His Leu His Trp His Thr Val Ala Lys Glu Thr CysSer Glu Lys 1 5 10 15 598 23 PRT Homo sapiens 598 His Met Asn Val GlnAsn Gly Lys Trp Glu Ser Asp Pro Ser Gly Thr 1 5 10 15 Lys Thr Cys IleGly Thr Lys 20 599 17 PRT Homo sapiens 599 His Met Asn Val Gln Asn GlyLys Trp Glu Ser Asp Pro Ser Gly Thr 1 5 10 15 Lys 600 19 PRT Humanimmunodeficiency virus 600 His Cys Leu Val Cys Phe Gln Lys Lys Gly LeuGly Ile Ser Tyr Gly 1 5 10 15 Arg Lys Lys 601 27 PRT Triticum aestivum601 His Lys Asp Arg Leu Thr Lys Lys Val Val Asp Ile Ala Arg Glu Val 1 510 15 Ala Lys Val Asp Val Pro Glu Tyr Arg Arg His 20 25 602 27 PRTTriticum aestivum 602 His Lys Glu Arg Leu Asp Arg Lys Val Val Asp ValAla Arg Glu Val 1 5 10 15 Ala Lys Val Glu Val Pro Ser Tyr Arg Arg His 2025 603 27 PRT Triticum aestivum 603 His Lys Glu Arg Leu Asp Arg Lys ValVal Asp Val Ala Arg Glu Val 1 5 10 15 Ala Lys Met Glu Val Pro Ser TyrArg Arg His 20 25 604 23 PRT Triticum aestivum 604 His Leu Gln Pro LysTrp Lys Pro Ser Leu Ser Trp Phe Lys Asn Ala 1 5 10 15 Glu Ser Arg LeuAsn His His 20 605 14 PRT Triticum aestivum 605 His Leu Gln Pro Lys TrpLys Pro Ser Leu Ser Trp Phe Lys 1 5 10 606 19 PRT Triticum aestivum 606Lys Trp Lys Pro Ser Leu Ser Trp Phe Lys Asn Ala Glu Ser Arg Leu 1 5 1015 Asn His His 607 18 PRT Triticum aestivum 607 Lys Trp Lys Pro Ser LeuSer Trp Phe Lys Asn Ala Glu Ser Arg Leu 1 5 10 15 Asn His 608 17 PRTTriticum aestivum 608 Lys Pro Ser Leu Ser Trp Phe Lys Asn Ala Glu SerArg Leu Asn His 1 5 10 15 His 609 16 PRT Triticum aestivum 609 Lys ProSer Leu Ser Trp Phe Lys Asn Ala Glu Ser Arg Leu Asn His 1 5 10 15 610 32PRT Triticum aestivum 610 His His Ala Ile Ala Leu Gly Leu His Thr ThrThr Leu Ile Leu Val 1 5 10 15 Lys Gly Ala Leu Asp Ala Arg Gly Ser LysLeu Met Pro Asp Lys Lys 20 25 30 611 31 PRT Triticum aestivum 611 HisAla Ile Ala Leu Gly Leu His Thr Thr Thr Leu Ile Leu Val Lys 1 5 10 15Gly Ala Leu Asp Ala Arg Gly Ser Lys Leu Met Pro Asp Lys Lys 20 25 30 61226 PRT Triticum aestivum 612 His His Ala Ile Ala Leu Gly Leu His Thr ThrThr Leu Ile Leu Val 1 5 10 15 Lys Gly Ala Leu Asp Ala Arg Gly Ser Lys 2025 613 25 PRT Triticum aestivum 613 His Ala Ile Ala Leu Gly Leu His ThrThr Thr Leu Ile Leu Val Lys 1 5 10 15 Gly Ala Leu Asp Ala Arg Gly SerLys 20 25 614 24 PRT Triticum aestivum 614 His Thr Thr Thr Leu Ile LeuVal Lys Gly Ala Leu Asp Ala Arg Gly 1 5 10 15 Ser Lys Leu Met Pro AspLys Lys 20 615 23 PRT Triticum aestivum 615 His Thr Thr Thr Leu Ile LeuVal Lys Gly Ala Leu Asp Ala Arg Gly 1 5 10 15 Ser Lys Leu Met Pro AspLys 20 616 18 PRT Triticum aestivum 616 His Thr Thr Thr Leu Ile Leu ValLys Gly Ala Leu Asp Ala Arg Gly 1 5 10 15 Ser Lys 617 44 PRT Triticumaestivum 617 His His His Leu Ala Ile Ala Ile Leu Phe Leu Ile Ala Gly HisMet 1 5 10 15 Tyr Arg Thr Asn Trp Gly Ile Gly His Gly Leu Lys Asp IleLeu Glu 20 25 30 Ala His Lys Gly Pro Phe Thr Gly Gln Gly His Lys 35 40618 43 PRT Triticum aestivum 618 His His Leu Ala Ile Ala Ile Leu Phe LeuIle Ala Gly His Met Tyr 1 5 10 15 Arg Thr Asn Trp Gly Ile Gly His GlyLeu Lys Asp Ile Leu Glu Ala 20 25 30 His Lys Gly Pro Phe Thr Gly Gln GlyHis Lys 35 40 619 42 PRT Triticum aestivum 619 His Leu Ala Ile Ala IleLeu Phe Leu Ile Ala Gly His Met Tyr Arg 1 5 10 15 Thr Asn Trp Gly IleGly His Gly Leu Lys Asp Ile Leu Glu Ala His 20 25 30 Lys Gly Pro Phe ThrGly Gln Gly His Lys 35 40 620 30 PRT Triticum aestivum 620 His Met TyrArg Thr Asn Trp Gly Ile Gly His Gly Leu Lys Asp Ile 1 5 10 15 Leu GluAla His Lys Gly Pro Phe Thr Gly Gln Gly His Lys 20 25 30 621 20 PRTTriticum aestivum 621 His Gly Leu Lys Asp Ile Leu Glu Ala His Lys GlyPro Phe Thr Gly 1 5 10 15 Gln Gly His Lys 20 622 17 PRT Triticumaestivum 622 Lys Asp Ile Leu Glu Ala His Lys Gly Pro Phe Thr Gly Gln GlyHis 1 5 10 15 Lys 623 11 PRT Triticum aestivum 623 His Lys Gly Pro PheThr Gly Gln Gly His Lys 1 5 10 624 10 PRT Triticum aestivum 624 Lys GlyPro Phe Thr Gly Gln Gly His Lys 1 5 10 625 16 PRT Oryza sativa 625 LysPhe Pro Asp Val Ile His Ala Phe Lys Pro Asn Pro Arg Ser His 1 5 10 15626 10 PRT Oryza sativa 626 Lys Phe Pro Asp Val Ile His Ala Phe Lys 1 510 627 10 PRT Oryza sativa 627 Lys Ala Arg Tyr Val Lys Phe His Trp Lys 15 10 628 33 PRT Oryza sativa 628 His Pro Lys Val Ser Pro Glu Leu Arg AlaIle Trp Val Asn Tyr Leu 1 5 10 15 Ser Gln Cys Asp Glu Ser Leu Gly ValLys Ile Ala Asn Leu Asn Val 20 25 30 Lys 629 45 PRT Oryza sativa 629 HisArg Asp Glu Glu Val Asp Tyr Tyr Pro Ser Arg His Ala Pro Leu 1 5 10 15Arg His Ala Pro Pro Thr Pro Ile Thr Pro Arg Pro Val Val Gly Arg 20 25 30Arg Gln Lys Ala Thr Ile His Lys Gln Asn Asp Phe Lys 35 40 45 630 11 PRTOryza sativa 630 Lys Ala Thr Ile His Lys Gln Asn Asp Phe Lys 1 5 10 63127 PRT Oryza sativa 631 His Ala Pro Pro Thr Pro Ile Pro Arg Pro Val ValGly Arg Arg Gln 1 5 10 15 Lys Ala Thr Ile His Lys Gln Asn Asp Phe Lys 2025 632 49 PRT Oryza sativa 632 Lys Phe Arg Pro Ser Ser Ser Phe Asp ThrLys Thr Thr Thr Thr Asn 1 5 10 15 Ala Gly Ala Pro Val Trp Asn Asp AsnGlu Ala Leu Thr Val Gly Pro 20 25 30 Arg Gly Pro Ile Leu Leu Glu Asp TyrHis Leu Ile Glu Lys Val Ala 35 40 45 His 633 42 PRT Oryza sativa 633 LysPhe Arg Pro Ser Ser Ser Phe Asp Thr Lys Thr Thr Thr Thr Asn 1 5 10 15Ala Gly Ala Pro Val Trp Asn Asp Asn Glu Ala Leu Thr Val Gly Pro 20 25 30Arg Gly Pro Ile Leu Leu Glu Asp Tyr His 35 40 634 9 PRT Oryza sativa 634Lys Val Lys Ala His Phe Gln Lys His 1 5 635 8 PRT Oryza sativa 635 LysVal Lys Ala His Phe Gln Lys 1 5 636 12 PRT Oryza sativa 636 Lys Asp TyrGlu Ile Asp Lys Asp Asp Leu Ile His 1 5 10 637 20 PRT Oryza sativa 637His Met Lys Gln Cys Phe Ala Phe Cys Ala Val Phe Pro Lys Asp Tyr 1 5 1015 Glu Ile Asp Lys 20 638 14 PRT Oryza sativa 638 His Met Lys Gln CysPhe Ala Phe Cys Ala Val Phe Pro Lys 1 5 10 639 49 PRT Oryza sativa 639His Val Phe Trp Glu Leu Val Trp Arg Ser Phe Phe Gln Asn Val Lys 1 5 1015 Gln Ile Gly Ser Ile Phe Gln Arg Lys Val Tyr Arg Tyr Gly Gln Ser 20 2530 Asp Val Thr Thr Ser Lys Ile His Asp Leu Met His Asp Leu Ala Val 35 4045 His 640 34 PRT Oryza sativa 640 Lys Gln Ile Gly Ser Ile Phe Gln ArgLys Val Tyr Arg Tyr Gly Gln 1 5 10 15 Ser Asp Val Thr Thr Ser Lys IleHis Asp Leu Met His Asp Leu Ala 20 25 30 Val His 641 29 PRT Oryza sativa641 Lys Gln Ile Gly Ser Ile Phe Gln Arg Lys Val Tyr Arg Tyr Gly Gln 1 510 15 Ser Asp Val Thr Thr Ser Lys Ile His Asp Leu Met His 20 25 642 25PRT Oryza sativa 642 Lys Gln Ile Gly Ser Ile Phe Gln Arg Lys Val Tyr ArgTyr Gly Gln 1 5 10 15 Ser Asp Val Thr Thr Ser Lys Ile His 20 25 643 9PRT Oryza sativa 643 Lys His Gly Val Ser Ala Gly Ile Lys 1 5 644 15 PRTOryza sativa 644 His Thr Val Phe Asp Tyr Gly Lys Met Arg Val Gly Phe AlaLys 1 5 10 15 645 17 PRT Oryza sativa 645 His Ser Arg Tyr Lys Ser GlyGln Ser Ser Thr Tyr Gln Lys Asn Gly 1 5 10 15 Lys 646 29 PRT Oryzasativa 646 Lys Gln Glu Ala Met Val Leu Lys Gln Glu Ile Asn Leu Leu GlnLys 1 5 10 15 Gly Leu Arg Tyr Ile Tyr Gly Asn Arg Ala Asn Glu His 20 25647 22 PRT Oryza sativa 647 Lys Gln Glu Ile Asn Leu Leu Gln Lys Gly LeuArg Tyr Ile Tyr Gly 1 5 10 15 Asn Arg Ala Asn Glu His 20 648 38 PRTOryza sativa 648 Lys Ser Lys Glu Gly Met Leu Lys Ala Ala Asn Glu Ile LeuGln Glu 1 5 10 15 Lys Ile Val Glu Gln Asn Gly Leu Ile Asp Val Gly MetMet Val Ala 20 25 30 Asp Gln Gln Asn Gly His 35 649 31 PRT Oryza sativa649 Lys Ala Ala Asn Glu Ile Leu Gln Glu Lys Ile Val Glu Gln Asn Gly 1 510 15 Leu Ile Asp Val Gly Met Met Val Ala Asp Gln Gln Asn Gly His 20 2530 650 11 PRT Zea mays 650 Lys Val Leu Ala Ala His Arg Tyr Gly Ile Lys 15 10 651 17 PRT Zea mays 651 Lys Leu Lys Ile Ala Met Lys His Leu Ile ProArg Val Leu Glu Gln 1 5 10 15 His 652 8 PRT Zea mays 652 Lys Leu Lys IleAla Met Lys His 1 5 653 33 PRT Zea mays 653 Lys Thr Ser Leu Ala Ser SerIle Ala Lys Ala Leu Asn Arg Lys Phe 1 5 10 15 Ile Arg Ile Ser Leu GlyGly Val Lys Asp Glu Ala Asp Ile Arg Gly 20 25 30 His 654 24 PRT Zea mays654 Lys Ala Leu Asn Arg Lys Phe Ile Arg Ile Ser Leu Gly Gly Val Lys 1 510 15 Asp Glu Ala Asp Ile Arg Gly His 20 655 19 PRT Zea mays 655 Lys PheIle Arg Ile Ser Leu Gly Gly Val Lys Asp Glu Ala Asp Ile 1 5 10 15 ArgGly His 656 37 PRT Zea mays 656 Lys Val Arg Leu Ser Lys Ala Thr Glu LeuVal Asp Arg His Leu Gln 1 5 10 15 Ser Ile Leu Val Ala Glu Lys Ile ThrGln Lys Val Glu Gly Gln Leu 20 25 30 Ser Lys Ser Gln Lys 35 657 24 PRTZea mays 657 His Leu Gln Ser Ile Leu Val Ala Glu Lys Ile Thr Gln Lys ValGlu 1 5 10 15 Gly Gln Leu Ser Lys Ser Gln Lys 20 658 14 PRT Zea mays 658Lys Val Arg Leu Ser Lys Ala Thr Glu Leu Val Asp Arg His 1 5 10 659 34PRT Zea mays 659 Lys Val Gly Gly Ser Ala Val Glu Ser Ser Lys Gln Asp ThrLys Asn 1 5 10 15 Gly Lys Glu Pro Ile His Trp His Ser Lys Gly Val AlaAla Arg Ala 20 25 30 Leu His 660 24 PRT Zea mays 660 Lys Val Gly Gly SerAla Val Glu Ser Ser Lys Gln Asp Thr Lys Asn 1 5 10 15 Gly Lys Glu ProIle His Trp His 20 661 22 PRT Zea mays 661 Lys Val Gly Gly Ser Ala ValGlu Ser Ser Lys Gln Asp Thr Lys Asn 1 5 10 15 Gly Lys Glu Pro Ile His 20662 24 PRT Zea mays 662 Lys Gln Asp Thr Lys Asn Gly Lys Glu Pro Ile HisTrp His Ser Lys 1 5 10 15 Gly Val Ala Ala Arg Ala Leu His 20 663 12 PRTZea mays 663 Lys Gln Asp Thr Lys Asn Gly Lys Glu Pro Ile His 1 5 10 66433 PRT Zea mays 664 His Arg Asp Leu Arg Arg Ala Arg Ala Ala Ala Leu AsnIle Val Pro 1 5 10 15 Thr Ser Thr Gly Ala Ala Lys Ala Val Ser Leu ValLeu Pro Asn Leu 20 25 30 Lys 665 18 PRT Zea mays 665 Lys Val Leu Asp GlnLys Phe Gly Ile Ile Lys Gly Thr Met Thr Thr 1 5 10 15 Thr His 666 16 PRTZea mays 666 His Ile Gln Ala Gly Ala Lys Lys Val Leu Ile Thr Ala Pro GlyLys 1 5 10 15 667 28 PRT Zea mays 667 His Gly Arg Gly Asp Ala Ser ProLeu Asp Val Ile Ala Ile Asn Asp 1 5 10 15 Thr Gly Gly Val Lys Gln AlaSer His Leu Leu Lys 20 25 668 51 PRT Zea mays 668 Lys Val Arg Arg ValLeu Ser Lys Asp Tyr Ser Ser Leu Lys Gln Leu 1 5 10 15 Met Thr Leu MetMet Asp Asp Asp Ile Ser Lys His Leu Gln Ile Ile 20 25 30 Glu Ser Gly LeuGlu Glu Arg Glu Asp Lys Val Trp Met Lys Glu Asn 35 40 45 Ile Ile Lys 50669 28 PRT Zea mays 669 Lys Val Arg Arg Val Leu Ser Lys Asp Tyr Ser SerLeu Lys Gln Leu 1 5 10 15 Met Thr Leu Met Met Asp Asp Asp Ile Ser LysHis 20 25 670 24 PRT Zea mays 670 His Leu Gln Ile Ile Glu Ser Gly LeuGlu Glu Arg Glu Asp Lys Val 1 5 10 15 Trp Met Lys Glu Asn Ile Ile Lys 20671 17 PRT Zea mays 671 His Asp Leu Arg Glu Asn Ile Ile Met Lys Ala AspAsp Leu Ala Ser 1 5 10 15 Lys 672 18 PRT Zea mays 672 His Val Gln AsnLeu Glu Asn Val Ile Gly Lys Asp Glu Ala Leu Ala 1 5 10 15 Ser Lys 673 21PRT Zea mays 673 Lys Lys Gln Gly Tyr Glu Leu Arg Gln Leu Lys Asp Leu AsnGlu Leu 1 5 10 15 Gly Gly Ser Leu His 20 674 20 PRT Zea mays 674 Lys GlnGly Tyr Glu Leu Arg Gln Leu Lys Asp Leu Asn Glu Leu Gly 1 5 10 15 GlySer Leu His 20 675 28 PRT Zea mays 675 Lys Leu Tyr Leu Lys Ser Arg LeuLys Glu Leu Ile Leu Glu Trp Ser 1 5 10 15 Ser Glu Asn Gly Met Asp AlaMet Asn Ile Leu His 20 25 676 39 PRT Zea mays 676 His Leu Gln Leu LeuGln Leu Asn Gly Met Val Glu Arg Leu Pro Asn 1 5 10 15 Lys Val Cys AsnLeu Ser Lys Leu Arg Tyr Leu Arg Gly Tyr Lys Asp 20 25 30 Gln Ile Pro AsnIle Gly Lys 35 677 31 PRT Zea mays 677 His Leu Gln Leu Leu Gln Leu AsnGly Met Val Glu Arg Leu Pro Asn 1 5 10 15 Lys Val Cys Asn Leu Ser LysLeu Arg Tyr Leu Arg Gly Tyr Lys 20 25 30 678 23 PRT Zea mays 678 His LeuGln Leu Leu Gln Leu Asn Gly Met Val Glu Arg Leu Pro Asn 1 5 10 15 LysVal Cys Asn Leu Ser Lys 20 679 14 PRT Zea mays 679 His Asn Ser Asn LysLeu Pro Lys Ser Val Gly Glu Leu Lys 1 5 10 680 11 PRT Zea mays 680 LysLeu Pro Lys Ser Val Gly Glu Leu Lys His 1 5 10 681 18 PRT Zea mays 681His Leu Ser Val Arg Val Glu Ser Met Gln Lys His Lys Glu Ile Ile 1 5 1015 Tyr Lys 682 8 PRT Zea mays 682 Lys His Lys Glu Ile Ile Tyr Lys 1 5683 23 PRT Zea mays 683 Lys Leu Arg Asp Ile Leu Gln Glu Ser Gln Lys PheLeu Leu Val Leu 1 5 10 15 Asp Leu Ala Leu Phe Lys His 20 684 46 PRT Zeamays 684 His Ala Phe Ser Gly Ala Glu Ile Lys Asp Gln Leu Leu Arg Met Lys1 5 10 15 Leu Gln Asp Thr Ala Glu Cys Ile Ala Lys Arg Leu Gly Gln CysPro 20 25 30 Leu Ala Ala Lys Val Leu Gly Ser Arg Met Cys Arg Arg Lys 3540 45 685 16 PRT Zea mays 685 His Ala Phe Ser Gly Ala Glu Ile Lys AspGln Leu Leu Arg Met Lys 1 5 10 15 686 47 PRT Zea mays 686 Lys Leu GlnAsp Thr Ala Glu Glu Ile Ala Lys Arg Leu Gly Gln Cys 1 5 10 15 Pro LeuAla Ala Lys Val Leu Gly Ser Arg Met Cys Arg Arg Lys Asp 20 25 30 Ile AlaGlu Trp Lys Ala Ala Asp Val Trp Phe Glu Lys Ser His 35 40 45 687 27 PRTZea mays 687 Lys Val Leu Gly Ser Arg Met Cys Arg Arg Lys Asp Ile Ala GluTrp 1 5 10 15 Lys Ala Ala Asp Val Trp Phe Glu Lys Ser His 20 25 688 17PRT Zea mays 688 Lys Asp Ile Ala Glu Trp Lys Ala Ala Asp Val Trp Phe GluLys Ser 1 5 10 15 His 689 11 PRT Zea mays 689 Lys Ala Ala Asp Val TrpPhe Glu Lys Ser His 1 5 10 690 40 PRT Zea mays 690 His Val Pro Thr ThrThr Ser Leu Pro Thr Ser Lys Val Phe Gly Arg 1 5 10 15 Asn Ser Asp ArgAsp Arg Ile Val Lys Phe Leu Leu Gly Lys Thr Thr 20 25 30 Thr Ala Glu AlaSer Ser Thr Lys 35 40 691 18 PRT Zea mays 691 Lys Ala Ile Leu Thr GluAla Lys Gln Leu Arg Asp Leu Leu Gly Leu 1 5 10 15 Pro His 692 29 PRT Zeamays 692 Lys Ala Lys Ala Lys Ser Gly Lys Gly Pro Leu Leu Arg Glu Asp Glu1 5 10 15 Ser Ser Ser Thr Ala Thr Thr Val Met Lys Pro Phe His 20 25 69329 PRT Zea mays 693 Lys Ser Pro His Arg Gly Lys Leu Glu Ser Trp Leu ArgArg Leu Lys 1 5 10 15 Glu Ala Phe Tyr Asp Ala Glu Asp Leu Leu Asp GluHis 20 25 694 16 PRT Zea mays 694 Lys Ser Pro His Arg Gly Lys Leu GluSer Trp Leu Arg Arg Leu Lys 1 5 10 15 695 13 PRT Zea mays 695 His ArgGly Lys Leu Glu Ser Trp Leu Arg Arg Leu Lys 1 5 10 696 7 PRT Zea mays696 Lys Ser Pro His Arg Gly Lys 1 5 697 8 PRT Zea mays 697 Lys Gln AlaSer His Leu Leu Lys 1 5 698 23 PRT Artificial Sequence Description ofArtificial Sequence Replikin formula sequence 698 Xaa Cys Xaa Xaa HisCys Xaa Xaa Cys Xaa Xaa Xaa Lys Xaa Leu Xaa 1 5 10 15 Xaa Xaa Xaa XaaArg Lys Lys 20 699 8 PRT Mycobacterium leprae 699 Lys Val Met Arg ThrAsp Lys His 1 5 700 17 PRT Mycobacterium tuberculosis 700 His Pro ArgPro Lys Val Ala Ala Ala Leu Lys Asp Ser Tyr Arg Leu 1 5 10 15 Lys 701 11PRT Mycobacterium tuberculosis 701 His Pro Arg Pro Lys Val Ala Ala AlaLeu Lys 1 5 10 702 19 PRT Mycobacterium tuberculosis 702 Lys Ser Ala GlnLys Trp Pro Asp Lys Phe Leu Ala Gly Ala Ala Gln 1 5 10 15 Val Ala His703 15 PRT Escherichia coli 703 His Ala Trp Gln His Gln Gly Lys Thr LeuPhe Ile Ser Arg Lys 1 5 10 15 704 11 PRT Escherichia coli 704 His GlnGly Lys Thr Leu Phe Ile Ser Arg Lys 1 5 10 705 19 PRT Agrobacteriumtumefaciens 705 His Ser Asp Gln Gln Leu Ala Val Met Ile Ala Ala Lys ArgLeu Asp 1 5 10 15 Asp Tyr Lys 706 33 PRT Agrobacterium tumefaciens 706His Leu Leu Asp His Pro Ala Ser Val Gly Gln Leu Asp Leu Arg Ala 1 5 1015 Met Leu Ala Val Glu Glu Val Lys Ile Asp Asn Pro Val Tyr Met Glu 20 2530 Lys 707 29 PRT Agrobacterium tumefaciens 707 His Pro Ala Ser Val GlyGln Leu Asp Leu Arg Ala Met Leu Ala Val 1 5 10 15 Glu Glu Val Lys IleAsp Asn Pro Val Tyr Met Glu Lys 20 25 708 39 PRT Agrobacteriumtumefaciens 708 Lys Cys Val Met Ala Lys Asn Cys Asn Ile Lys Cys Pro AlaGly Leu 1 5 10 15 Thr Thr Asn Gln Glu Ala Phe Asn Gly Asp Pro Arg AlaLeu Ala Gln 20 25 30 Tyr Leu Met Asn Ile Ala His 35 709 34 PRTAgrobacterium tumefaciens 709 Lys Asn Cys Asn Ile Lys Cys Pro Ala GlyLeu Thr Thr Asn Gln Glu 1 5 10 15 Ala Phe Asn Gly Asp Pro Arg Ala LeuAla Gln Tyr Leu Met Asn Ile 20 25 30 Ala His 710 27 PRT Agrobacteriumtumefaciens 710 His His Asp Thr Tyr Ser Ile Glu Asp Leu Ala Gln Leu IleHis Asp 1 5 10 15 Ala Lys Ala Ala Arg Val Arg Val Ile Val Lys 20 25 71126 PRT Agrobacterium tumefaciens 711 His Asp Thr Tyr Ser Ile Glu Asp LeuAla Gln Leu Ile His Asp Ala 1 5 10 15 Lys Ala Ala Arg Val Arg Val IleVal Lys 20 25 712 13 PRT Agrobacterium tumefaciens 712 His Asp Ala LysAla Ala Arg Val Arg Val Ile Val Lys 1 5 10 713 42 PRT Agrobacteriumtumefaciens 713 Lys Ile Gly Gln Gly Ala Lys Pro Gly Glu Gly Gly Gln LeuPro Ser 1 5 10 15 Pro Lys Val Thr Val Glu Ile Ala Ala Ala Arg Gly GlyThr Pro Gly 20 25 30 Val Glu Leu Val Ser Pro Pro Pro His His 35 40 71441 PRT Agrobacterium tumefaciens 714 Lys Ile Gly Gln Gly Ala Lys Pro GlyGlu Gly Gly Gln Leu Pro Ser 1 5 10 15 Pro Lys Val Thr Val Glu Ile AlaAla Ala Arg Gly Gly Thr Pro Gly 20 25 30 Val Glu Leu Val Ser Pro Pro ProHis 35 40 715 46 PRT Agrobacterium tumefaciens 715 Lys Ala Ser Glu IleThr Lys Thr Leu Ala Ser Gly Ala Met Ser His 1 5 10 15 Gly Ala Leu ValAla Ala Ala His Glu Ala Val Ala His Gly Thr Asn 20 25 30 Met Val Gly GlyMet Ser Asn Ser Gly Glu Gly Gly Glu His 35 40 45 716 29 PRTAgrobacterium tumefaciens 716 Lys Ala Ser Glu Ile Thr Lys Thr Leu AlaSer Gly Ala Met Ser His 1 5 10 15 Gly Ala Leu Val Ala Ala Ala His GluAla Val Ala His 20 25 717 24 PRT Agrobacterium tumefaciens 717 Lys AlaSer Glu Ile Thr Lys Thr Leu Ala Ser Gly Ala Met Ser His 1 5 10 15 GlyAla Leu Val Ala Ala Ala His 20 718 16 PRT Agrobacterium tumefaciens 718Lys Ala Ser Glu Ile Thr Lys Thr Leu Ala Ser Gly Ala Met Ser His 1 5 1015 719 27 PRT Agrobacterium tumefaciens 719 Lys Arg Tyr Phe Pro Asn ValLys Thr Pro Val Gly Gly Val Thr Phe 1 5 10 15 Ala Val Ile Ala Gln AlaVal Ala Asp Trp His 20 25 720 48 PRT Agrobacterium tumefaciens 720 HisHis Ile Ala Ala Gly Leu Gly Phe Gly Ala Ser Ala Val Tyr Pro 1 5 10 15Leu Gly Val Gln Phe Arg Ala Glu Glu Lys Phe Gly Ala Asp Ala Asp 20 25 30Lys Ala Phe Lys Arg Phe Ala Lys Ala Ala Glu Lys Ser Leu Met Lys 35 40 45721 48 PRT Agrobacterium tumefaciens 721 His His Ile Ala Ala Gly Leu GlyPhe Gly Ala Ser Ala Val Tyr Pro 1 5 10 15 Leu Gly Val Gln Phe Arg AlaGlu Glu Lys Phe Gly Ala Asp Ala Asp 20 25 30 Lys Ala Phe Lys Arg Phe AlaLys Ala Ala Glu Lys Ser Leu Met Lys 35 40 45 722 44 PRT Agrobacteriumtumefaciens 722 His His Ile Ala Ala Gly Leu Gly Phe Gly Ala Ser Ala ValTyr Pro 1 5 10 15 Leu Gly Val Gln Phe Arg Ala Glu Glu Lys Phe Gly AlaAsp Ala Asp 20 25 30 Lys Ala Phe Lys Arg Phe Ala Lys Ala Ala Glu Lys 3540 723 40 PRT Agrobacterium tumefaciens 723 His His Ile Ala Ala Gly LeuGly Phe Gly Ala Ser Ala Val Tyr Pro 1 5 10 15 Leu Gly Val Gln Phe ArgAla Glu Glu Lys Phe Gly Ala Asp Ala Asp 20 25 30 Lys Ala Phe Lys Arg PheAla Lys 35 40 724 33 PRT Agrobacterium tumefaciens 724 His His Ile AlaAla Gly Leu Gly Phe Gly Ala Ser Ala Val Tyr Pro 1 5 10 15 Leu Gly ValGln Phe Arg Ala Glu Glu Lys Phe Gly Ala Asp Ala Asp 20 25 30 Lys 725 47PRT Agrobacterium tumefaciens 725 His Ile Ala Ala Gly Leu Gly Phe GlyAla Ser Ala Val Tyr Pro Leu 1 5 10 15 Gly Val Gln Phe Arg Ala Glu GluLys Phe Gly Ala Asp Ala Asp Lys 20 25 30 Ala Phe Lys Arg Phe Ala Lys AlaAla Glu Lys Ser Leu Met Lys 35 40 45 726 43 PRT Agrobacteriumtumefaciens 726 His Ile Ala Ala Gly Leu Gly Phe Gly Ala Ser Ala Val TyrPro Leu 1 5 10 15 Gly Val Gln Phe Arg Ala Glu Glu Lys Phe Gly Ala AspAla Asp Lys 20 25 30 Ala Phe Lys Arg Phe Ala Lys Ala Ala Glu Lys 35 40727 39 PRT Agrobacterium tumefaciens 727 His Ile Ala Ala Gly Leu Gly PheGly Ala Ser Ala Val Tyr Pro Leu 1 5 10 15 Gly Val Gln Phe Arg Ala GluGlu Lys Phe Gly Ala Asp Ala Asp Lys 20 25 30 Ala Phe Lys Arg Phe Ala Lys35 728 32 PRT Agrobacterium tumefaciens 728 His Ile Ala Ala Gly Leu GlyPhe Gly Ala Ser Ala Val Tyr Pro Leu 1 5 10 15 Gly Val Gln Phe Arg AlaGlu Glu Lys Phe Gly Ala Asp Ala Asp Lys 20 25 30 729 28 PRTAgrobacterium tumefaciens 729 Lys Phe Gly Leu Tyr Asp Ala Ala Phe GluLys Ser Ser Cys Gly Val 1 5 10 15 Gly Phe Ile Thr Arg Lys Asp Gly ValGln Thr His 20 25

What is claimed is:
 1. An isolated or synthesized peptide comprisingfrom 7 to about 50 amino acids comprising: (1) at least one lysineresidue located six to ten residues from a second lysine residue; (2) atleast one histidine residue; and (3) at least 6% lysine residues.
 2. Theisolated or synthesized peptide of claim 1 wherein said peptide aminoacid sequence comprises between 7 to 25 amino acids residues.
 3. Theisolated or synthesized peptide of claim 1 wherein said peptide aminoacid sequence comprises between 7 to 16 amino acid residues.
 4. Anisolated or synthesized viral peptide comprising from 7 to about 50amino acids comprising: (1) at least one lysine residue located six toten residues from a second lysine residue; (2) at least one histidineresidue; and (3) at least 6% lysine residues.
 5. The peptide of claim 4wherein said peptide is an influenza virus peptide.
 6. The peptide ofclaim 4 wherein said peptide is a human immunodeficiency virus (HIV)peptide.
 7. The peptide of claim 4, wherein said viral peptide is anhepatitis virus.
 8. The peptide of claim 4 wherein said viral peptide isa maize streak virus peptide.
 9. The peptide of claim 4 wherein saidviral peptide is a herpes virus peptide.
 10. The peptide of claim 4wherein said viral peptide is a bovine herpes virus peptide. 11 Thepeptide of claim 4 wherein said viral peptide is a meleagrid herpesvirus peptide.
 12. The peptide of claim 4 wherein said viral peptide isa feline immunodeficiency virus peptide.
 13. The peptide of claim 4wherein said viral peptide is a foot and mouth disease virus peptide.14. The peptide of claim 4 wherein said viral peptide is a rous sarcomavirus peptide.
 15. The peptide of claim 4 wherein said viral peptide isan avian sarcoma virus peptide.
 16. The peptide of claim 4 wherein saidviral peptide is a neuroblastoma RAS viral oncogene peptide.
 17. Thepeptide of claim 4 wherein said viral peptide is a polyoma viruspeptide.
 18. The peptide of claim 4 wherein said viral peptide is asindbis peptide.
 19. The peptide of claim 4 wherein said viral peptideis a human papilloma virus peptide.
 20. The peptide of claim 4 whereinsaid viral peptide is a myelomonocytic tumor virus peptide.
 21. Thepeptide of claim 4 wherein said viral peptide is a murine acute leukemiapeptide.
 22. The peptide of claim 4 wherein said viral peptide is ahuman T-cell lymphotropic virus peptide.
 23. The peptide of claim 4wherein said viral peptide is a tomato leaf curl virus peptide.
 24. Thepeptide of claim 6 wherein said HIV viral peptide is a HIVtrans-activator peptide.
 25. The peptide according to claim 24 whereinsaid viral peptide has the sequence as set forth in SEQ ID NO:
 600. 26.An isolated bacterial peptide comprising from 7 to about 50 amino acidsincluding: (1) at least one lysine residue located six to ten residuesfrom a second lysine residue; (2) at least one histidine residue; and(3) at least 6% lysine residues.
 27. The peptide of claim 26 whereinsaid bacterial peptide is a Helicobacter peptide.
 28. The peptide ofclaim 27 wherein said Helicobacter peptide is a Helicobacter pyloripeptide.
 29. The peptide of claim 26 wherein said bacterial peptide is aStahylococcus peptide.
 30. The peptide of claim 29 wherein saidStaphylococcus peptide is a Staphylococcus aureus peptide.
 31. Thepeptide of claim 26 wherein said bacterial peptide is a Legionellapeptide.
 32. The peptide of claim 31 wherein said Legionella peptide isa Legionella pneumophilia peptide.
 33. The peptide of claim 26 whereinsaid bacterial peptide is a Acetobacter peptide.
 34. The peptide ofclaim 26 wherein said bacterial peptide is a Actinomyces peptide. 35.The peptide of claim 26 wherein said bacterial peptide is a Aerobacterpeptide.
 36. The peptide of claim 26 wherein said bacterial peptide is aArthrobacter peptide.
 37. The peptide of claim 26 wherein said bacterialpeptide is a Azotobacter peptide.
 38. The peptide of claim 26 whereinsaid bacterial peptide is a Bacillus peptide.
 39. The peptide of claim26 wherein said bacterial peptide is a Brevibacterium.
 40. The peptideof claim 26 wherein said bacterial peptide is a Clostridium peptide. 41.The peptide of claim 26 wherein said bacterial peptide is aCorynebacterium peptide.
 42. The peptide of claim 26 wherein saidbacterial peptide is a Erwinia peptide.
 43. The peptide of claim 26wherein said bacterial peptide is a Escheria peptide.
 44. The peptide ofclaim 26 wherein said bacterial peptide is a Klebsiella peptide.
 45. Thepeptide of claim 26 wherein said bacterial peptide is a Lactobacilluspeptide.
 46. The peptide of claim 26 wherein said bacterial peptide is aHaemophilus peptide.
 47. The peptide of claim 26 wherein said bacterialpeptide is a Flavobacterium peptide.
 48. The peptide of claim 26 whereinsaid bacterial peptide is a Methylomonas peptide.
 49. The peptide ofclaim 26 wherein said bacterial peptide is a Micrococcus peptide. 50.The peptide of claim 26 wherein said bacterial peptide is aMycobacterium peptide.
 51. The peptide of claim 26 wherein saidbacterial peptide is a Micronomspora peptide.
 52. The peptide of claim26 wherein said bacterial peptide is a Mycoplasma peptide.
 53. Thepeptide of claim 26 wherein said bacterial peptide is a Neisseriapeptide.
 54. The peptide of claim 26 wherein said bacterial peptide is aNocardia peptide.
 55. The peptide of claim 26 wherein said bacterialpeptide is a Proteus peptide.
 56. The peptide of claim 26 wherein saidbacterial peptide is a Pseudomonas peptide.
 57. The peptide of claim 26wherein said bacterial peptide is a Rhizobium peptide.
 58. The peptideof claim 26 wherein said bacterial peptide is a Salmonella peptide. 59.The peptide of claim 26 wherein said bacterial peptide is a Serratiapeptide.
 60. The peptide of claim 26 wherein said bacterial peptide is aStaphylococcus peptide.
 61. The peptide of claim 26 wherein saidbacterial peptide is a Streptocossus peptide.
 62. The peptide of claim26 wherein said bacterial peptide is a Streptomyces peptide.
 63. Thepeptide of claim 26 wherein said bacterial peptide is aStreptosporangium peptide.
 64. The peptide of claim 26 wherein saidbacterial peptide is a Streptovirticillium peptide.
 65. The peptide ofclaim 26 wherein said bacterial peptide is a Vibrio peptide.
 66. Thepeptide of claim 26 wherein said bacterial peptide is a Xanthomaspeptide.
 67. An isolated or synthesized fungal peptide comprising from 7to about 50 amino acids comprising: (1) at least one lysine residuelocated six to ten residues from a second lysine residue; (2) at leastone histidine residue; and (3) at least 6% lysine residues.
 68. Thepeptide of claim 67 wherein said fungal peptide is a Penicilliumpeptide.
 69. The peptide of claim 67 wherein said fungal peptide is aDiseula Peptide.
 70. The peptide of claim 67 wherein said fungal peptideis a Ophiostoma peptide.
 71. The peptide of claim 70 wherein saidOphiostoma peptide is a Ophiostoma novo-ulmi peptide.
 72. The peptide ofclaim 67 wherein said fungal peptide is a Candida peptide.
 73. Thepeptide of claim 67 wherein said fungal peptide is a Absidia peptide.74. The peptide of claim 67 wherein said fungal peptide is a AspergillusPeptide.
 75. The peptide of claim 67 wherein said fungal peptide is aCephalosporium peptide.
 76. The peptide of claim 67 wherein said fungalpeptide is a Fusarium peptide.
 77. The peptide of claim 67 wherein saidfungal peptide is a Hansenula peptide.
 78. The peptide of claim 67wherein said fungal peptide is a Mucor peptide.
 79. The peptide of claim67 wherein said fungal peptide is a Paecilomyces peptide.
 80. Thepeptide of claim 68 wherein said Penicillium peptide is a Penicilliummarneffei peptide.
 81. The peptide of claim 67 wherein said fungalpeptide is a Pichia peptide.
 82. The peptide of claim 67 wherein saidfungal peptide is a Rhizopus peptide.
 83. The peptide of claim 67wherein said fungal peptide is a Saccharomyces peptide.
 84. The peptideof claim 67 wherein said fungal peptide is a Torulopsis peptide.
 85. Thepeptide of claim 67 wherein said fungal peptide is a Trichodermapeptide.
 86. The peptide of claim 67 wherein said fungal peptide is aErysiphe peptide.
 87. The peptide of claim 67 wherein said fungalpeptide is a Phytophthora infestans peptide.
 88. An isolated orsynthesized algal peptide comprising from 7 to about 50 amino acidscomprising: (1) at least one lysine residue located six to ten residuesfrom a second lysine residue; (2) at least one histidine residue; and(3) at least 6% lysine residues.
 89. The peptide of claim 88 whereinsaid algal peptide is a Caldophera peptide.
 90. The peptide of claim 88wherein said algal peptide is a Isolepisprolifera peptide.
 91. Thepeptide of claim 88 wherein said algal peptide is a Porphyra peptide.92. The peptide of claim 88 wherein said algal peptide is a Chondruspeptide.
 93. The peptide of claim 88 wherein said algal peptide is aGracilaria peptide.
 94. The peptide of claim 88 wherein said algalpeptide is a Gelidium peptide.
 95. The peptide of claim 88 wherein saidalgal peptide is a Caulerpa peptide.
 96. The peptide of claim 88 whereinsaid algal peptide is a Laurencia peptide.
 97. The peptide of claim 88wherein said algal peptide is a Cladophexa peptide.
 98. The peptide ofclaim 88 wherein said algal peptide is a Sargassum peptide.
 99. Thepeptide of claim 88 wherein said algal peptide is a Penicillos peptide.100. The peptide of claim 88 wherein said algal peptide is a Halimedapeptide.
 101. The peptide of claim 88 wherein said algal peptide is aLaminaria peptide.
 102. The peptide of claim 88 wherein said algalpeptide is a Fucus peptide.
 103. The peptide of claim 88 wherein saidalgal peptide is a Ascophyllum peptide.
 104. The peptide of claim 88wherein said algal peptide is a Undari peptide.
 105. The peptide ofclaim 88 wherein said algal peptide is a Rhodymenia peptide.
 106. Thepeptide of claim 88 wherein said algal peptide is a Macrocystis peptide.107. The peptide of claim 88 wherein said algal peptide is a Eucheumapeptide.
 108. The peptide of claim 88 wherein said algal peptide is aAhnfeltia peptide.
 109. The peptide of claim 88 wherein said algalpeptide is a Pteroclasia peptide.
 110. An isolated or synthesized yeastpeptide comprising from 7 to about 50 amino acids including: (1) atleast one lysine residue located six to ten residues from a secondlysine residue; (2) at least one histidine residue; and (3) at least 6%lysine residues.
 111. The peptide of claim 110 wherein said yeastpeptide is a Saccharomyces peptide.
 112. The peptide of claim 110wherein said yeast peptide is a Cryptococcus peptide.
 113. The peptideof claim 110 wherein said Cryptococcus peptide is a Cryptococcusneoformas peptide.
 114. The peptide of claim 110 wherein said yeastpeptide is a Schizosaccharomyces peptide.
 115. The peptide of claim 110wherein said yeast peptide is a Oryza peptide.
 116. An isolated orsynthesized amoeba peptide comprising from 7 to about 50 amino acidscomprising: (1) at least one lysine residue located six to ten residuesfrom a second lysine residue; (2) at least one histidine residue; and(3) at least 6% lysine residues.
 117. The peptide of claim 116 whereinsaid amoeba peptide is an Entamoeba invadens peptide.
 118. The peptideof claim 116 wherein said amoeba peptide is an Amoebidae peptide. 119.The peptide of claim 116 wherein said amoeba peptide is an Acanthamoebapeptide.
 120. The peptide of claim 116 wherein said amoeba peptide is anNaegleria peptide.
 121. An isolated or synthesized plant peptidecomprising from 7 to about 50 amino acids comprising: (1) at least onelysine residue located six to ten residues from a second lysine residue;(2) at least one histidine residue; and (3) at least 6% lysine residues.122. The peptide of claim 121 wherein said plant peptide is a wheatpeptide.
 123. The peptide of claim 121 wherein said plant peptide is arice peptide.
 124. The peptide of claim 121 wherein said plant peptideis a maize peptide.
 125. The peptide of claim 122 wherein said wheatpeptide is a Ubiquitin activating enzyme peptide.
 126. The peptide ofclaim 125 wherein said wheat peptide is a PsaB wheat peptide.
 127. Thepeptide of claim 125 wherein said wheat peptide is a PsaA wheat peptide.128. An isolated or synthesized structural replication-associatedpeptide comprising from 7 to about 50 amino acids comprising: (1) atleast one lysine residue located six to ten residues from a secondlysine residue; (2) at least one histidine residue; and (3) at least 6%lysine residues.
 129. The peptide of claim 128 wherein said structuralreplication-associated peptide is a PMC1 peptide.
 130. The peptide ofclaim 128 wherein said structural replication-associated peptide is anucleolar scleroderma antigen.
 131. The peptide of claim 128 whereinsaid structural replication-associated peptide is a fibrillarin peptide.132. The peptide of claim 128 wherein said structuralreplication-associated peptide is a SPOP peptide.
 133. The peptide ofclaim 128 wherein said structural replication-associated peptide is aCentromere protein C peptide.
 134. The peptide of claim 128 wherein saidstructural replication-associated peptide is a CTCBF, KU antigenpeptide.
 135. The peptide of claim 128 wherein said structuralreplication-associated peptide is an ATP synthase peptide.
 136. Thepeptide of claim 128 wherein said structural replication-associatedpeptide is a FBRL nuclear peptide.
 137. The peptide of claim 128 whereinsaid structural replication-associated peptide is a HP1Hs-alpha peptide.138. The peptide of claim 128 wherein said structuralreplication-associated peptide is a PM/Scl nucleolar peptide.
 139. Thepeptide of claim 128 wherein said structural replication-associatedpeptide is an amyloid beta A4 precursor peptide.
 140. An isolated orsynthesized tumor virus associated peptide comprising from 7 to about 50amino acids including: (1) at least one lysine residue located six toten residues from a second lysine residue; (2) at least one histidineresidue; and (3) at least 6% lysine residues.
 141. An isolated orsynthesized transforming-associated peptide comprising from 7 to about50 amino acids including: (1) at least one lysine residue located six toten residues from a second lysine residue; (2) at least one histidineresidue; and (3) at least 6% lysine residues. transforming-associatedpeptide.
 142. An isolated or synthesized cancer-cell associated peptidecomprising from 7 to about 50 amino acids including: (1) at least onelysine residue located six to ten residues from a second lysine residue;(2) at least one histidine residue; and (3) at least 6% lysine residues.The peptide of claim 1 wherein said peptide is a cancer cell associatedpeptide.
 143. A method for increasing the replication rate of anorganism comprising transforming a gene encoding an enzyme or otherprotein having a replication function in the organism with at least oneReplikin structure.
 144. The method of claim 143 wherein the organism isa food plant.
 145. The method of claim 144 wherein the organism is arice plant.
 146. The method of claim 144 wherein the organism is a wheatplant.
 147. The method of claim 144 wherein the organism is a maizeplant
 148. An antibody that specifically binds to a viral peptidesequence having from 7 to about 50 amino acids and including: (1) atleast one lysine residue located six to ten residues from a secondlysine residue; (2) at least one histidine residue; and (3) at least 6%lysine residues.
 149. A composition comprising the antibody of claim 148and a pharmaecutically acceptable carrier or adjuvant.
 150. An antibodythat specifically binds to a bacterial peptide sequence having from 7 toabout 50 amino acids and including: (1) at least one lysine residuelocated six to ten residues from a second lysine residue; (2) at leastone histidine residue; and (3) at least 6% lysine residues.
 151. Acomposition comprising the antibody of claim 150 and a pharmaceuticallyacceptable carrier or adjuvant.
 152. An antibody that specifically bindsto a fungal peptide sequence having from 7 to about 50 amino acids andincluding: (1) at least one lysine residue located six to ten residuesfrom a second lysine residue; (2) at least one histidine residue; and(3) at least 6% lysine residues.
 153. A composition comprising theantibody of claim 152 and a pharmaecutically acceptable carrier oradjuvant.
 154. An antibody that specifically binds to a yeast peptide orpolypeptide sequence comprising from 7 to about 50 amino acidsincluding: (1) at least one lysine residue located six to ten amino acidresidues from a second lysine residue; (2) at least one histidineresidue; and (3) at least 6% lysine residues.
 155. A compositioncomprising the antibody of claim 154 and a pharmaecutically acceptablecarrier or adjuvant
 156. An antibody that specifically binds to anamoeba peptide or polypeptide sequence comprising from 7 to about 50amino acids including: (1) at least one lysine residue located six toten amino acid residues from a second lysine residue; (2) at least onehistidine residue; and (3) at least 6% lysine residues.
 157. Acomposition comprising the antibody of claim 156 and a pharmaecuticallyacceptable carrier or adjuvant.
 158. An antibody cocktail comprising aplurality of antibodies, wherein each of the antibodies specificallybinds to a viral peptide sequence comprising from 7 to about 50 aminoacids and including: (1) at least one lysine residue located six to tenresidues from a second lysine residue; (2) at least one histidineresidue; and (3) at least 6% lysine residues.
 159. An antibody cocktailcomprising a plurality of antibodies, wherein each of the antibodiesspecifically binds to a bacterial peptide sequence comprising from 7 toabout 50 amino acids and including: (1) at least one lysine residuelocated six to ten residues from a second lysine residue; (2) at leastone histidine residue; and (3) at least 6% lysine residues.
 160. Anantibody cocktail comprising a plurality of antibodies, wherein each ofthe antibodies specifically binds to a fungal peptide sequencecomprising from 7 to about 50 amino acids and including: (1) at leastone lysine residue located six to ten residues from a second lysineresidue; (2) at least one histidine residue; and (3) at least 6% lysineresidues.
 161. An antibody cocktail comprising a plurality ofantibodies, wherein each of the antibodies specifically binds to a yeastpeptide sequence comprising from 7 to about 50 amino acids andincluding: (1) at least one lysine residue located six to ten residuesfrom a second lysine residue; (2) at least one histidine residue; and(3) at least 6% lysine residues.
 162. An antibody cocktail comprising aplurality of antibodies, wherein each of the antibodies specificallybinds to a amoeba peptide sequence comprising from 7 to about 50 aminoacids and including: (1) at least one lysine residue located six to tenresidues from a second lysine residue; (2) at least one histidineresidue; and (3) at least 6% lysine residues.
 163. A process forstimulating the immune system of a subject to produce antibodies thatbind specifically to viral Replikins, said process comprisingadministering to the subject an effective amount of a dosage of acomposition comprising at least one viral Replikin peptide.
 164. Aprocess for stimulating the immune system of a subject to produceantibodies that bind specifically to viral Replikins, said processcomprising administering to the subject an effective amount of a dosageof a composition comprising at least one non-immune-based organic agentthat specifically targets bacterial Replikin sequences.
 165. The processof claim 164 wherein the agent is nucleic acid.
 166. The process ofclaim 165 wherein the nucleic acid is in antisense configuration. 167.The process of claim 164 wherein the dosage is administered as anapproximately 1 mg dosage form.
 168. A dual treatment method of treatingmalaria comprising: (1) administering an effective amount of at leastone proteolytic enzyme; and (2) administering an effective amount of atleast one antibody specific for at least one isolated Plasmodiumfalciparum Replikin peptide having from 7 to about 50 amino acids andincluding: (1) at least one lysine residue located six to ten residuesfrom a second lysine; (2) at least one histidine; and (3) at least 6%lysine residues.
 169. The method of claim 168 wherein a plurality ofantibodies specific for Plasmodium falciparum Replikins areadministered.
 170. A method of treating malaria comprising: (1)administering an effective amount of at least one proteolytic enzyme;and (2) administering an effective amount of a preventive or therapeuticvaccine comprising at least one isolated Plasmodium falciparum Replikinpeptide having from 7 to about 50 amino acids and including: (1) atleast one lysine residue located six to ten residues from a secondlysine; (2) at least one histidine; and (3) at least 6% lysine residues.171. The method of claim 170 wherein the vaccine comprises a pluralityof Replikins specific for Plasmodium falciparum.
 172. The method ofclaim 170 wherein the vaccine comprises overlapping Replikins.
 173. Amethod to recognize a Replikin peptide structure called the “three-pointrecognition method” whereby the Replikin peptide is composed of fromseven (7) to about (50) amino acids and include: (1) at least one lysineresidue located six to ten residues from a second lysine; (2) at leastone histidine; and (3) at least 6% lysine residues.